BDNF

Ketogenic diet raises brain blood flow by 22% and increases brain-derived neurotrophic factor by 47%, highlighting its potential to support cognitive function even in people without cognitive impairment. pubmed.ncbi.nlm.nih.gov

Brain Diet Ketosis Memory BDNF Ketogenic Diet

Glucose has long been considered the brain’s primary fuel, but ketone bodies may offer critical support, especially during periods of low carbohydrate availability. A recent study found that a ketogenic diet boosted levels of brain-derived neurotrophic factor (BDNF)—a key protein that supports brain health—by 47%, highlighting the diet’s potential to support brain health even in people without cognitive impairment.

Researchers recruited 11 healthy but overweight adults to participate in a randomized, crossover study. Each participant followed two different diets: a ketogenic diet high in fat and low in carbohydrates, and a standard balanced diet. Each diet lasted three weeks and ended with brain imaging scans (using MRI and PET) and blood tests to measure brain blood flow and BDNF levels.

They found that the ketogenic diet markedly increased ketone levels in the blood compared to the standard diet. Brain blood flow rose by 22% after eating the ketogenic diet, and BDNF levels increased by 47%. Researchers also found a strong link between ketone levels in the blood and higher brain blood flow.

This was a small study, but the findings suggest that a ketogenic diet enhances brain blood flow and boosts vital brain-supporting proteins, even in people without memory loss. This opens up new possibilities for using ketogenic nutrition as a strategy to preserve cognitive function and support long-term brain health. Learn how to plan the optimal ketogenic diet in this clip featuring Dr. Dominic D'Agostino.

Uphill walking, even at a slow pace, provides cognitive benefits by increasing brain lactate and stimulating BDNF production—a protein critical for memory and learning. www.sciencedirect.com

Exercise Brain Memory BDNF Lactate

If you’re struggling to remember things, a robust workout might help. Scientists have discovered that exercise can increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports learning and memory. A recent study in rats found that low-speed uphill exercise raises blood lactate levels, increasing lactate and BDNF in key brain regions involved in cognition.

Researchers divided rats into three groups: One remained inactive, another walked on a flat treadmill, and a third walked uphill at a 40% incline. The exercise sessions lasted either 30 or 90 minutes. To see if lactate from the blood contributed to brain changes, some rats also received a direct lactate injection.

Uphill exercise increased lactate levels in the animals' blood and brains, while flat treadmill walking did not. After 90 minutes, uphill exercise also raised BDNF levels in brain regions linked to memory and learning. The lactate injection showed that blood lactate passed into the brain, reinforcing that exercise-induced increases in blood lactate can influence brain chemistry.

These findings suggest that walking uphill—even slowly—provides cognitive benefits by raising brain lactate and stimulating BDNF production. This type of exercise could be a practical and safe way to support brain health, especially for older adults or those looking to enhance memory and learning. To learn more strategies to boost brain health, check out the Cognitive Enhancement Blueprint, a member-only perk.

High-intensity training outperforms moderate exercise in boosting cognitive function. bmcsportsscimedrehabil.biomedcentral.com

Exercise Brain Dementia BDNF

The connection between physical exercise and enhanced cognitive function is well-established. However, the extent of benefit varies markedly depending on the intensity of the physical activity. A recent study found that high-intensity interval training (HIIT) boosted reaction time and cognitive flexibility better than moderate-intensity continuous exercise (MICE).

The study involved 28 elite male boxers in their mid-twenties. The participants underwent cognitive performance tests and provided blood samples in five scenarios: after an hour of rest, immediately after HIIT, one hour after HIIT, immediately after MICE, and one hour after MICE.

The blood tests revealed that participants' serum brain-derived neurotrophic factor (BDNF) levels immediately after exercise were considerably higher after HIIT than after rest or MICE. Interestingly, serum levels of S100B and neuron-specific enolase (proteins associated with brain injury) were also higher after HIIT than after rest but were comparable to those after MICE. HIIT and MICE improved cognitive performance, but HIIT was better at improving reaction time and incongruent task assessments (which measure cognitive flexibility).

These findings suggest that HIIT and MICE elicit beneficial effects on the brain, with HIIT outperforming MICE in certain arenas. These effects may be attributable to increased BDNF, a growth factor known to influence neuronal health and mediate the beneficial cognitive effects associated with exercise. Learn more about BDNF in the Cognitive Enhancement Blueprint, located in the Members' Library.

BDNF emerges as a critical marker of omega-3 fatty acid levels in the brain. www.nature.com

Brain Omega-3 BDNF

The Omega-3 Index measures omega-3 fatty acid concentrations in red blood cells. It provides a reliable assessment of long-term intake and is highly reflective of fatty acid composition in most tissues, with one notable exception – the brain. A recent study suggests that brain-derived neurotrophic factor (BDNF), a protein involved in learning and memory, is a more reliable measure of brain omega-3 concentrations than the Omega-3 Index.

Researchers gave rats and mice different types and amounts of supplemental omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and dietary fish and krill oils. Then, they measured the fatty acids in the animals' red blood cells (Omega-3 Index) and the BDNF concentrations in their plasma and brain tissues.

They found that increased brain omega-3 levels were positively associated with elevated plasma BDNF but inversely associated with red blood cell concentrations, suggesting that plasma BDNF is a more dependable biomarker than the Omega-3 Index for evaluating the effectiveness of omega-3 supplementation and dietary intake in enhancing brain function.

BDNF is critical for brain function, neurogenesis, neuronal survival, memory, and body weight regulation. Low BDNF concentrations are typical in psychiatric disorders but typically rise after antidepressant treatment and high omega-3 fatty acid doses. Exercise and DHA-rich diets also elevate BDNF, and some evidence suggests that BDNF mediates DHA’s beneficial brain effects.

Learn more about the Omega-3 Index in our stub article.

Physical activity may protect women against Parkinson's disease. www.medscape.com

Exercise Parkinson's Inflammation BDNF

Parkinson’s disease is a neurodegenerative disorder that affects the central nervous system. New research suggests that exercise reduces the risk of developing Parkinson’s disease. Women who regularly engaged in physical activity were 25 percent less likely to develop the disease than inactive women.

Researchers gathered information about the lifestyles and medical histories of more than 99,000 women and categorized them according to their activity levels. Then, using a statistical method that accounted for the reduced activity that might precede a diagnosis of Parkinson’s disease, they investigated the effects of exercise on Parkinson’s disease risk.

They found that physical activity levels were consistently lower in women who developed Parkinson’s disease than in those who did not, even up to 29 years before the disease was diagnosed. The difference between the two groups became more pronounced around 10 years before diagnosis. Overall, women with the highest activity levels had a 25 percent lower risk of developing Parkinson’s disease than those with the least activity, even after considering other risk factors.

These findings suggest that exercise protects women against Parkinson’s disease. The mechanisms that drive this protective effect may be related to exercise’s capacity to regulate key neurotransmitters, promote the release of brain-derived neurotrophic factor (BDNF), ameliorate brain inflammation, and reduce oxidative stress. Interestingly, exercise also benefits people after they have been diagnosed with Parkinson’s disease. Learn more in this clip featuring Dr. Giselle Petzinger.

Read full publication.

Exercise and supplemental lactate may improve cognitive function. www.nature.com

Exercise Brain Dementia BDNF Lactate

Lactate boosts cognitive function in mice, according to a new study. Mice had better spatial working and long-term memory after exercising and receiving supplemental lactate.

Researchers studied the effects of exercise – with or without supplemental lactate – on cognitive function in mice. The mice engaged in moderate-intensity exercise (about 55 to 60 percent of their VO2 max) five days a week for five weeks. This level of intensity is just below the “lactate threshold” – the point at which lactate builds up in the bloodstream and compromises performance. At the end of the five-week period, they tested the animals' memory skills.

They found that exercise plus supplemental lactate improved the animals' spatial working and long-term memory. In addition, the expression of various proteins produced in the hippocampus, including FNDC5 (also called irisin) and brain-derived neurotrophic factor (BDNF), increased, suggesting that supplemental lactate augments the beneficial effects of exercise on the hippocampus and subsequent cognitive function.

Lactate is a compound produced in muscles during exercise via the breakdown of glucose. It is thought to participate in a sort of “lactate shuttle” in which it is transported from the muscles into tissues like the heart and brain, where it is used for energy. Evidence suggests that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal BDNF expression. Learn more about the lactate shuttle and its effects on the brain in this episode featuring Dr. George Brooks.

Read full publication.

Greater, more intense physical activity may preserve brain volume – especially in the hippocampus, an area of the brain involved in memory. Physichttps://neurosciencenews.com/physical-activity-neuroprotection-21177/al activity boosts brain health.

Exercise Aging BDNF Blood-Brain Barrier

Being more physically active is associated with having larger brain volume, a 2022 study found. The greatest brain-enhancing effects were seen in those who engaged in moderate- to vigorous-intensity exercises.

The study involved more than 2,500 adults between the ages of 30 and 94 years. The participants wore wrist accelerometers to track their activity levels and underwent brain scans to assess their brain volume, cortical thickness, and gray matter density.

The scans revealed that physical activity had a marked, dose-dependent effect on the participants' brain health. Those with greater, more intense physical activity levels exhibited larger brain volumes – especially in the hippocampus, an area of the brain involved in memory – than those with lower, less intense levels. However, the beneficial effects of physical activity on brain health were particularly evident when comparing the brain volumes of those who engaged in moderate physical activity to those who were sedentary, suggesting that even small increases in physical activity can boost brain health and reduce brain volume losses associated with aging.

The beneficial effects of physical activity may be related to exercise-induced production of brain-derived neurotrophic factor (BDNF), a protein that controls and promotes the growth of new neurons. BDNF is active in the hippocampus, cortex, cerebellum, and basal forebrain – areas involved in learning, long term memory, and executive function. Learn more about the brain-boosting effects of BDNF in our comprehensive overview article.

Read study abstract.

Lactate produced from high-intensity exercise may play crucial memory role and correlates closely with plasma BDNF. www.mdpi.com

Exercise Brain Aerobic BDNF Neurodegeneration Lactate

From the article:

Current research has shown that (i) increased peripheral lactate levels (following high intensity exercise) are associated with increased peripheral BDNF levels, (ii) lactate infusion at rest can increase peripheral and central BDNF levels and (iii) lactate plays a very complex role in the brain’s metabolism. In this review, we summarize the role and relationship of lactate and BDNF in exercise induced neuroplasticity.

[…]

Several trials have used blood lactate for the monitoring of exercise intensity. These studies indicate that higher lactate concentrations are associated with increased BDNF plasma and/or serum levels. Furthermore, current evidence indicates that high intensity interval training evokes larger BDNF levels compared to moderate and/or intensive continuous exercise […] Current research indicates that lactate transport from astrocytes to neurons plays a crucial role for memory formation and could be a link between exercise and neuroplasticity. Pharmacological inhibition of MCT 2 irreversibly impairs long-term memory. Van de Hall et al. have shown that lactate uptake in the brain increases from 8% at rest up to 20% during exercise.

Just six minutes of vigorous exercise a day may be sufficient to protect the brain against Alzheimer's disease and cognitive decline. medicalxpress.com

Exercise Brain Alzheimer's BDNF

Six minutes of vigorous exercise increased brain levels of BDNF – a protein that may protect against Alzheimer’s disease and other neurodegenerative conditions – as much as five times more than light exercise, a new study has found.

Researchers measured BDNF levels after fasting, light exercise, or vigorous exercise in healthy, physically active adults. Participants fasted for 20 hours, engaged in light cycling (90 minutes at 25 percent VO2 max), or engaged in vigorous cycling (six 40-second bursts at 100 percent VO2 max interspersed with 20 seconds of light cycling).

They found that on average, 90 minutes of light cycling increased serum BDNF levels by approximately 6 percent. However, six 40-second vigorous-intensity cycling bursts increased both plasma and serum BDNF levels four to five times more than light cycling.

BDNF, or brain-derived neurotrophic factor, is a growth factor that controls and promotes the growth of new neurons and is necessary for the formation and storage of memories and overall cognitive performance. BDNF exerts robust protective effects on crucial neuronal circuitry involved in Alzheimer’s disease. Evidence suggests that endothelial cells that line the blood vessels of the brain release BDNF in response to shear stress – the increase in force that occurs during increased blood flow (as in exercise).

Interestingly, fasting for 20 hours had no effect on BDNF levels, but it did promote a ninefold increase in ketone delivery to the brain. Evidence suggests that ketones increase blood flow to the brain and improve memory and brain function in certain contexts. Learn more about the brain benefits of ketones in this clip featuring Dr. Dominic D'Agostino.

Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com

Brain Hormones Memory Mental Health Anxiety Genetics Estrogen Schizophrenia BDNF

From the article:

The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.

The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.

View full publication

Estradiol may induce BDNF/TrkB signaling in non-estrogen-dependent breast cancer to promote brain metastases, mouse study suggests. (2019) www.sciencedaily.com

Brain Cancer Hormones Breast Cancer Estrogen BDNF

From the article:

After all, triple negative breast cancers lack estrogen receptors (along with progesterone receptors and HER2, thus the name triple negative), and so these cancers can’t possibly be influenced by estrogen. Right?

[…]

Technically, Cittelly and colleagues including postdoctoral researcher, Maria Contreras-Zarate, PhD, found that estrogen induces astrocytes (brain cells) to produce growth factors called brain-derived neurotrophic factor (BDNF) and Epidermal Growth Factor (EGF), and that these factors turns on two genetic migration/invasion switches in cancer cells, namely TRKB and EGFR.

“This may explain why breast cancers diagnosed in younger women are more likely to metastasize to the brain – pre-menopausal women have more estrogen, and it may be influencing the microenvironment of the brain in ways that aid cancer,” Cittelly says.

View full publication

Neuron-derived estrogen may regulate synaptic plasticity and memory, mouse study suggests. (2019) www.sciencedaily.com

Hormones Memory Neurotransmitter Estrogen BDNF

From the article:

Brann and his colleagues found that mice whose neurons don’t make estrogen have impaired spatial reference memory – like a baseball player not knowing where home plate is and what it means to get there – as well as recognition memory and contextual fear memory – so they have trouble remembering what’s hazardous – they report in the Journal of Neuroscience.

Restoring estrogen levels to the brain area rescues these impaired functions, Brann and his colleagues report.

It was known that aromatase, the enzyme that converts testosterone to estrogen, was made in the brain’s hippocampus and cerebral cortex in a variety of species that includes humans, Brann says, and that they all can have memory deficits when aromatase is blocked. Patients who take an aromatase inhibitor for estrogen-dependent breast cancer also have reported memory problems.

[…]

Knocking out aromatase also decreased expression of CREB, a major transcription factor known to play a key role in learning and memory, the scientists write, as well as neuron-nourishing brain derived neurotrophic factor, or BDNF.

[…]

The scientists say these findings implicate neuron-derived estrogen as a novel neuromodulator, basically a critical messenger one neuron relies on to communicate with others, which is essential to key functions like cognition.

View full publication

Neuron-derived estrogen may be critical for astrocyte activation and neuroprotection of the ischemic brain, mouse study suggests. (2020) www.sciencedaily.com

Hormones Estrogen BDNF Stroke

From the article:

In the face of low brain oxygen that can occur with stroke or other brain injury, these astrocytes, star-shaped brain cells that help give the brain its shape and regularly provide fuel and other support to neurons, should become “highly reactive,” increasing cell signaling, releasing neuroprotective factors and clearing neurotoxins, scientists report in The Journal of Neuroscience.

[…]

To try to understand how astrocytes take on this enhanced role, they knocked out the enzyme aromatase, which is critical to estrogen production, in neurons in the forebrain, the largest region of the human brain, in their animal model.

They found that one way estrogen made by neurons is protective in ischemia is by suppressing signaling of the fibroblast growth factor, FGF2, which is also made by neurons and known to suppress astrocyte activation, Brann and his colleagues write. Normally neurons use this FGF2 brake to help keep astrocyte response from getting out of control.

[…]

In this scenario, when they used a neutralizing antibody to block FGF2, astrocytes became more active and neuron damage was decreased. “The astrocyte activation came back and we saw the protective growth factors that they make,” Brann says. Giving more estrogen produced similar benefits, including improving cognition after ischemia.

[…]

They also saw less of known neuroprotective growth factors, like brain derived neurotrophic factor and insulin-like growth factor 1, which astrocytes normally release at an increased rate in response to a stressor like ischemia, and more suppressive substances like the brake FGF2 [when the estrogen producing enzyme aromatase was knocked out].

[…]

Activated astrocytes also help clear glutamate, the brain’s most abundant excitatory neurotransmitter that normally helps neurons communicate. But without estrogen from the neurons, the glutamate transporter, GLT-1, which removes about 90% of the glutamate, is significantly decreased and the chemical can accumulate at toxic levels in the brain and become a major cause of neuron destruction. “Glutamate is essential for brain function, but if it’s overproduced, it’s brain toxic,” Brann says.

View full publication

Aerobic exercise improves working memory and promotes BDNF production. www.frontiersin.org

Exercise BDNF

Adolescents who engage in aerobic physical activity tend to have better cardiometabolic health and perform better in school. Unfortunately, most adolescents fall short of recommended physical activity guidelines. Findings from a recent study suggest that aerobic physical activity improves working memory and promotes the production of BDNF in adolescent girls.

BDNF, or brain-derived neurotrophic factor, is a growth factor that controls and promotes the growth of new neurons. It is active in areas of the brain involved in learning, long-term memory, and executive function. Robust evidence indicates that aerobic exercise increases BDNF concentrations.

The study involved 16 healthy adolescent girls (average age, 11 years). Half of the girls engaged in three sprint-training sessions for two weeks, while the other half continued their regular physical activities. The investigators measured the girls' metabolic biomarkers, BDNF concentrations, and working memory before and after the intervention.

They found that compared to the girls who continued their regular activities, the girls who engaged in the two weeks of sprint training performed 2.2 percent better on memory tests, and their BDNF concentrations nearly doubled. Neither group exhibited differences in their metabolic biomarkers. The girls who participated in the sprint training reported enjoying the activities.

These findings suggest that aerobic exercise programs not only improve cognitive function and increase BDNF concentrations in adolescent girls, but they are also enjoyable. Learn more about the beneficial effects of aerobic exercise in our overview article.

Whole-body hyperthermia activates muscle hormone irisin and increases neuroprotective factors. www.sciencedirect.com

Exercise Brain Muscle Sauna BDNF Neurodegeneration

Exposure to high heat while sauna bathing causes mild hyperthermia – an increase in the body’s core temperature – that induces a thermoregulatory response to restore homeostasis and condition the body for future heat stressors. These adaptations to high temperatures involve increased production of brain derived neurotrophic factor (BDNF), a promoter of neuroplasticity, and irisin, a biomarker of exercise. Findings of a new report demonstrate that whole-body hyperthermia increases BDNF and irisin in healthy young adults.

Whole-body hyperthermia is a therapeutic strategy used to treat various diseases, including cancer and depression. Previous research has shown that use of a hyperthermia chamber increases BDNF to a greater extent than light intensity exercise. Some research has suggested that BDNF production is stimulated by irisin, a hormone secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise and sauna use in humans, but additional research is needed.

The authors recruited 20 male participants (average age, 22 years) and assessed their baseline heat tolerance using a hyperthermia protocol. Participants reclined in a hyperthermia chamber while the researchers increased the temperature of the chamber by 50 degrees F every ten minutes until the participant reached their personal heat threshold. Next, participants completed ten hyperthermia sessions tailored to their baseline conditioning, during which the hyperthermia chamber was set to a temperature of 150 to 175 degrees F. Following a three-week wash-out period, they completed ten sham treatments over two weeks, during which the hyperthermia chamber was set to a temperature of 75 to 77 degrees F.

Participants had an average core body temperature of 102 degrees F at the end of each whole-body hyperthermia treatment. Following ten whole-body hyperthermia treatments, participants had a significant increase in circulating irisin levels (6.3 micrograms per milliliter) compared to their baseline levels (5.0 micrograms per milliliter) and compared to their irisin levels following the sham treatment (5.4 micrograms per milliliter). Whole-body hyperthermia treatment also significantly increased BDNF levels (28.3 picograms per liter) compared to baseline (25.9 picograms per liter).

In healthy young adults, ten whole-body hyperthermia significantly increased irisin and BDNF levels. The authors noted that future studies should explore the effects of whole-body hyperthermia on adipose tissue, which also produces irisin.

Decreased brain derived neurotrophic factor, physical activity, and brain volume are associated with greater memory impairment. www.nature.com

Brain Aging BDNF

Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of pro-BDNF and memory loss.

The effects of Alzheimer’s disease on the brain can be observed 10 to15 years before the onset of dementia, which presents the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides the ability for early intervention.

The authors recruited 256 older adults (average age, 68 years) without dementia. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory and physical activity habits.

The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Finally, the authors reported that decreased blood levels of BDNF, but not pro-BDNF, were associated with worse memory performance.

These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors conclude the measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

Suicidal behavior linked to Val66Met genetic variant which reduces BDNF activity www.sciencedaily.com

Brain Depression Behavior BDNF

From the article:

After pooling results from 11 previous studies and adding their own study data involving people with schizophrenia, CAMH scientists confirmed that among people with a psychiatric diagnosis, those with the methionine (“met”) variation of the gene had a higher risk of suicidal behaviour compared to those with the valine variation.

[…]

“Our findings may lead to the testing and development of treatments that target this gene in order to help prevent suicide,” says Dr. James Kennedy, director of CAMH’s Neuroscience Research Department. “In the future, if other researchers can replicate and extend our findings, then genetic testing may be possible to help identify people at increased risk for suicide.”

As the low-functioning BDNF met variation is a risk factor for suicidal behaviour, it may also be possible to develop a compound to increase BDNF functioning, Dr. Kennedy says.

The brain-derived neurotrophic factor gene in suicidal behaviour: a meta-analysis.

A loss of BDNF, as a result of viral strategy, may be responsible for a type of dementia that occurs in 30 percent of untreated HIV-positive patients www.sciencedaily.com

Brain HIV Dementia BDNF

From the article:

The research team found that even though HIV does not infect neurons, it tries to stop the brain from producing a protein growth factor – mature brain derived neurotrophic factor (mature BDNF) – that Mocchetti says acts like “food” for brain neurons.

[…]

Mocchetti believes that HIV stops production of mature BDNF because that protein interferes with the ability of the virus to attack other brain cells. It does this through the potent gp120 envelope protein that sticks out from the viral shell – the same protein that hooks on to brain macrophages and microglial cells to infect them. “In earlier experiments, when we dumped gp120 into neuronal tissue culture, there was a 30-40 percent loss of neurons overnight. That makes gp120 a remarkable neurotoxin.”

Human Immunodeficiency Virus Type 1 Alters Brain-Derived Neurotrophic Factor Processing in Neurons

Lithium blocks some of the sleep disturbances, memory loss, and learning problems tied to fetal alcohol syndrome in mouse study www.sciencedaily.com

Sleep Alcohol Memory Pregnancy Development Lithium BDNF

From the article:

The new study found that giving the drug to newborn mice 15 minutes after “binge” alcohol consumption eliminated the hyperactivity and sleep deficits seen when rodents exposed to alcohol became adults. Moreover, the researchers report, lithium chloride-treated mice were much less likely to show the 25 percent drop in memory and cognitive test scores seen in untreated mice given the same amount of alcohol.

“Our study showed that lithium chloride prevented many of the damaging neurological effects of alcohol abuse on the still-developing brain, especially the impact on the parts of the brain controlling sleep,” says co-senior study investigator Donald Wilson, PhD.

Promoting BDNF as one pathway to brain cell survival:

“Lithium chloride is known to block many pathways that lead to brain cell death, while promoting others that lead to survival, like brain-derived neurotrophic factor, or BDNF,” says Saito, a research assistant professor at NYU Langone. Further experiments are needed, she says, to determine if chemicals that stimulate BDNF production also blunt the effects of alcohol abuse in newborn mammals.

Note: increased BDNF seems to actually be a natural mechanism by which the brain responds to reduce damage of BDNF

The combination of tobacco and alcohol may exacerbate deleterious effects in memory region: increased oxidative stress in hippocampus, less BDNF www.sciencedaily.com

Brain Alcohol Memory Tobacco BDNF

From the article:

The researchers treated rats with alcohol, tobacco smoke or both twice a day for 28 days and then compared their brains with control animals that didn’t receive either substance. They found that the combined alcohol and smoking treatment increased the level of reactive oxygen species in the hippocampus compared with control animals or rats given tobacco smoke alone. In all of the brain areas studied, combined alcohol and smoking increased the levels of specific pro-inflammatory cytokines more than either treatment alone.

Reduced levels of BDNF, another harbinger of bad news:

And in the striatum and frontal cortex, rats with both treatments showed lower levels of brain-derived neurotrophic factor, a growth factor that helps existing neurons survive and stimulates the growth of new ones. These results suggest that alcoholics who smoke could be at additional risk for neural damage, the researchers say.

20-minute transcranial direct current stimulation sessions shown to enhance maze performance, memory, brain plasticity in rodent model of Alzheimer's www.sciencedaily.com

Brain Alzheimer's BDNF Neurodegeneration

From the article:

After exposing the mice to single 20-minute tDCS sessions, the researchers saw signs of improved memory and brain plasticity (the ability to form new connections between neurons when learning new information), which lasted at least a week. This intellectual boost was demonstrated by the enhanced performance of the mice during tests requiring them to navigate a water maze and distinguish between known and unknown objects.

This effect depended on increased production of BDNF:

More important, the researchers identified the actual molecular trigger behind the bolstered memory and plasticity–increased production of BDNF, a protein essential to brain growth. BDNF, which stands for “brain-derived neurotrophic factor,” is synthesized naturally by neurons and is crucial to neuronal development and specialization.

“While the technique and behavioral effects of tDCS are not new,” said ONR Global Associate Director Dr. Monique Beaudoin, “Dr. Grassi’s work is the first to describe BDNF as a mechanism for the behavioral changes that occur after tDCS treatment. This is an exciting and growing research area of great interest to ONR.”

Publication

BDNF variant may mediate degree of brain benefits from exercise. www.sciencedaily.com

Exercise Brain Memory ADHD BDNF

Exercise improves cognitive function and reduces the risk neurodegenerative diseases such as Alzheimer’s disease. Some of these benefits are mediated by brain-derived neurotrophic factor (BDNF). Findings from a 2012 study showed that regular exercise improved cognitive function and increased BDNF levels, but a genetic variant in BDNF influenced the degree of these effects.

BDNF is a protein that acts on neurons in the central and peripheral nervous systems. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. This genetic variant, known as Val66Met, alters exercise-driven release of BDNF and affects learning, memory, and emotion.

The intervention study involved 75 sedentary, healthy, young adults between the ages of 18 and 35 years. The participants took memory tests and mental health surveys before and after engaging in their randomly assigned respective activities: no exercise; four weeks of exercise with exercise and a test on the last day; four weeks of exercise, without exercise on the final test day; or a single bout of exercise on the last test day.

The participants who engaged in exercise showed improvements in memory and experienced lower levels of perceived stress, but only if they exercised for four weeks including the final day of testing. Participants who engaged in a single bout of exercise showed no changes in memory performance and demonstrated higher perceived stress levels. The authors of the study noted improvements in the participants' memory only if they did not carry the Val66Met variant, suggesting that the associated reduction in BDNF release attenuated some of the cognitive benefits of exercise. They also noted that the improvements in cognitive function were not correlated to improvements in mental health.

These findings suggest that the variable effects of exercise on brain function are related to a genetic variant that influences the production of BDNF.

Link to full study.

Omega-3 DHA intake increases hypothalamic neurogenesis in mice. diabetes.diabetesjournals.org

Brain Obesity Omega-3 BDNF

Saturated fatty acid intake induces inflammation in the hypothalamus that can eventually lead to apoptosis of hypothalamic neurons and subsequent loss of the control of caloric intake and energy expenditure. The overall health of hypothalamic neurons requires their regular renewal, a process known as neurogenesis, which is impaired in obesity. Findings from a 2016 study showed that docosahexaenoic acid (DHA), a type of polyunsaturated fatty acid (PUFA), increased hypothalamic neurogenesis in mice.

DHA is an omega-3 fatty acid found in the human brain and the meat of fatty fish. DHA plays a key role in the development of eye and nerve tissues and is essential for normal brain function in humans.

The authors of the study conducted a six-protocol study in mice. They fed the mice a high-fat diet for eight weeks and then fed them diets containing varying concentrations and types of fats, including flaxseed oil and DHA. They also injected DHA or BDNF, a growth factor involved in neurogenesis, into the brains of the mice.

Mice that ate the DHA-containing diet showed improvements in body mass, glucose metabolism, activity levels, and response to leptin, a hormone involved in appetite control. Both the DHA-containing diet and the injected DHA increased levels of hypothalamic neurogenesis at rates similar to or superior to those observed with BDNF.

These findings suggest that dietary intake of PUFAs such as DHA show promise as a strategy to ameliorate hypothalamic neuronal losses associated with obesity.

Link to full study.

Dance intervention increased brain volume and plasma BDNF levels in older adults. pubmed.ncbi.nlm.nih.gov

Brain BDNF

Aging alters many features of brain structure and function. Emerging evidence indicates that these alterations are avoidable, however. Findings from a 2018 study demonstrate that dancing counteracts the harmful effects of aging on the human brain.

Previous research has demonstrated that dancing simultaneously challenges sensory, motor, and cognitive aspects of brain function. Dancing is comparable to other forms of exercise in terms of cardiovascular demands, but it differs in terms of coordinative and cognitive demands.

The authors of the study randomized 38 adults between the ages of 63 and 80 years to participate in one of two six-month-long exercise programs. Half of the participants engaged in active but repetitive exercises such as cycling and weight training, and the other half engaged in dancing. Both groups participated in their respective activities twice a week for 90 minutes. The authors of the study collected blood samples, performed cognitive and physical fitness assessments, and conducted imaging studies to determine the participants' responses to the interventions.

The participants who engaged in the dance intervention showed marked improvements in brain volume in several regions of their brains compared to the other group, especially in the cingulate cortex, insula, corpus callosum and sensorimotor cortex, areas responsible for emotion, learning, memory, self-awareness, and voluntary movement. Both groups showed improvements in attention and spatial memory, but dancing increased the participants' plasma BDNF levels. BDNF is a growth factor that plays key roles in neuroplasticity, the brain’s capacity to reorganize itself in response to changes in its environment.

These findings suggest that dance is superior to other forms of active exercise in terms of brain benefits. Exercise intervention programs geared toward older adults show promise as a means to forestall the harmful effects of aging on the brain.

Link to full study.

Fish oil omega-3 normalizes BDNF levels in the hippocampus and improves cognitive function in animal model of traumatic brain injury www.liebertpub.com

Brain Omega-3 Tissue Repair BDNF TBI

From the publication:

Our finding that supplementation of omega-3 fatty acids normalizes the protein levels of BDNF after TBI suggests that BDNF mediates the beneficial effects of omega-3 fatty acids on cognitive function.

[…]

It is notable that fish oil supplementation increased BDNF but did not affect cognitive function in intact rats. It is possible that slight changes in BDNF may not significantly affect cognition under normal conditions. It seems likely, however, that under pathological weakness small decreases in BDNF can be a factor to further deteriorate cognitive function. This eventual possibility emphasizes the necessity to use therapeutic means, such as dietary supplementation of fish oil, to maintain normal levels of BDNF under challenging conditions.

Mitigation of oxidative stress as a mechanism of increased BDNF:

It has been shown that TBI can result in cumulative ROS, which may be associated with reduction of BDNF. Thus, DHA may help to counteract elevated levels of ROS with subsequent effects on the action of BDNF on synaptic plasticity and cognition after TBI.

BDNF genetic variant Val66met found in ~30% of the population is associated with up to 20% worse performance on driving test www.sciencedaily.com

Brain Genetics BDNF

From the article:

People with a particular gene variant performed more than 20 percent worse on a driving test than people without it – and a follow-up test a few days later yielded similar results. About 30 percent of Americans have the variant.

Often there are benefits and trade-offs when it comes to genetics:

The gene variant isn’t always bad, though. Studies have found that people with it maintain their usual mental sharpness longer than those without it when neurodegenerative diseases such as Parkinson’s, Huntington’s and multiple sclerosis are present.

“It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”

Publication

Carriers of a common BDNF genetic variant demonstrate more rapid decline from Alzheimer's disease. www.sciencedaily.com

Brain Alzheimer's Genetics BDNF Neurodegeneration

BDNF plays critical roles in many aspects of cognitive function, including learning and memory formation. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in a specific region of the DNA where the gene is located. Evidence suggests that carrying the Met allele (Met/Met or Val/Met genotype) is associated with lower BDNF expression.. A 2017 study found that amyloid-beta burden impaired BDNF-related learning and memory.

Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

The study involved more than 1,000 adults (approximately 55 years at the beginning of the study) who were enrolled in a larger study of Alzheimer’s disease. Nearly 65 percent of the participants were at high risk for developing Alzheimer’s disease, having at least one parent diagnosed with the condition. Each of the participants underwent cognitive assessment and BDNF genotyping five times over a period of four to 11 years. In addition, a small cohort of participants underwent imaging studies to assess amyloid-beta burden.

The genotyping revealed that approximately one-third of the participants were carriers of the Met-66 allele. Compared to Val/Val carriers, Met-66 carriers showed steeper declines in cognitive function. In addition, Met-66 carriers with greater amyloid-beta burden showed an even greater cognitive decline, likely due to lower BDNF expression. These findings suggest that a SNP in the gene for BDNF influences cognitive health and could serve as a therapeutic target against Alzheimer’s disease.

Link to full study.

BDNF delivery via hydrogel improves respiratory function in rats with spinal cord injury. www.sciencedaily.com

Tissue Repair BDNF

Approximately 17,000 people living in the United States will experience traumatic spinal cord injury in any given year. A severe complication associated with spinal cord injury is the loss of respiratory function, which often occurs due to paralysis of the diaphragm muscle. A 2018 study showed that BDNF delivery to the injured spinal cord improved respiratory function in rats.

Previous research has demonstrated that systemic delivery of neurotrophic factors is associated with many undesirable side effects, such as muscle spasms and chronic pain, and exerts reduced efficacy. The authors of the current study used a water-based gel to deliver a solution of polysaccharide-BDNF particles to spinal cord-injured female rats. This delivery mode keeps the BDNF at the site of injury instead of allowing it to become more widely distributed. Then they measured the action potential in the rats' diaphragm muscle.

They found that the BDNF hydrogel improved diaphragm muscle contractility by more than 60 percent, likely due to BDNF-mediated protection and/or restoration of neurons that innervate the diaphragm.

These findings suggest that targeted delivery of BDNF is a viable strategy for preserving respiratory function following traumatic spinal cord injury.

Link to full study.

From the blood to the brain: BDNF-producing blood cells travels to the hypothalamus in adults, regulating and suppressing appetite [animal research] www.sciencedaily.com

Brain Obesity BDNF

From the article:

We knew that blood cells produced BDNF,“[…] "We didn’t know why it was produced in blood cells.”

Dr. Hiroshi Urabe and Dr. Hideto Kojima, current and former postdoctoral fellows in Chan’s laboratory respectively, looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain’s hypothalamus called the paraventricular nucleus.

“We knew that in embryonic development, some blood cells do go to the brain and become microglial cells,” said Chan. […]“This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells.”

A new way to affect appetite and obesity?

When normal bone marrow cells that produce BDNF are injected into the third ventricle (a fluid-filled cavity in the brain) of mice that lack BDNF, they no longer have the urge to overeat, said Chan.

All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity, said Chan.

He and his colleagues hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion’s share of the work.

Publication

BDNF mimetic 7,8-dihydroxyflavone protects neurons against cell death. www.sciencedaily.com

Brain Parkinson's BDNF Stroke

BDNF’s neuroprotective capacity suggests that it could be useful in preventing or treating neurodegenerative diseases. Circumventing problems with BDNF’s delivery, half-life, and other limitations has proven challenging. A 2010 study found that 7,8-dihydroxyflavone, a BDNF mimetic, exerted neuroprotective qualities similar to those of BDNF.

7,8-dihydroxyflavone is a type of flavonoid compound present in a variety of plants. Flavonoids exert antioxidant and anti-inflammatory effects, among others. Some evidence indicates that 7,8-dihydroxyflavone might be useful in reversing the damage associated with lead poisoning in children.

The authors of the study screened 2,000 bioactive compounds to gauge their ability to protect rodent and human neurons from apoptosis and identified five compounds, including 7,8-dihydroxyflavone, that showed potential in protecting the cells. Then they treated the cells with BDNF and the various compounds and deprived the cells of oxygen and glucose.

They found that none of the compounds was as effective as 7,8-dihydroxyflavone in protecting the cells from apoptosis. In fact, 7,8-dihydroxyflavone was even more protective than BDNF. They also found that 7,8-dihydroxyflavone exerted its protective qualities by activating a receptor called TrkB, to which BDNF binds. They replicated their findings in an in vivo study of mice, indicating that 7,8-dihydroxyflavone enhances neuronal survival.

These findings demonstrate that flavonoid compounds that mimic the effects of BDNF show potential as therapeutics against neurodegenerative diseases.

Link to full study.

Plasma levels of BDNF lower in women with history of suicide attempts. www.sciencedaily.com

Brain Depression BDNF

Suicide is a major public health concern, claiming the lives of nearly 800,000 people worldwide each year. A history of a suicide attempt is a robust predictor of a future attempt. Findings from a 2017 study suggest that plasma levels of BDNF are a marker for suicidality.

BDNF is a protein that plays critical roles in the creation and functioning of neurons and the ability of synapses to strengthen or weaken over time. Low BDNF levels are associated with an increased risk for depression.

The participants in the study included 34 women with a history of suicide attempt and 39 without (average age, 33 years). The women were matched based on age, ethnicity, family income, body mass index, and cigarette smoking history. The authors of the study assessed the women’s mental health history and current status and took blood samples to determine BDNF levels.

Thirty (88 percent) of the women who had attempted suicide had a lifetime history of major depressive disorder. Of these, 14 (40 percent) met the criteria for current major depressive disorder. The women with a history of suicide attempt had lower levels of BDNF than women without a history of suicide – a difference that was maintained even after taking into account other potential psychiatric or demographic factors. The authors of the study posited that lower BDNF levels represent a trait-like biochemical indicator of suicide risk and might be relevant for suicide prevention.

Other biochemical indicators of suicide have been identified, as well. For example, markers of accelerated extrinsic aging have been observed in the blood of suicide completers. Age acceleration is a phenomenon that occurs when an individual’s epigenetic age exceeds their chronological age. Learn more about epigenetic aging in this overview article.

Link to study abstract.

BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com

Brain Alcohol Genetics Addiction BDNF

Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.

BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.

Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.

The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.

The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.

These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.

Link to study abstract.

Bipolar disorder patients experience generalized impaired cellular resilience and broad reductions in BDNF that may contribute to the disease www.sciencedaily.com

Brain Depression Stress BDNF

From the article:

Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in bipolar disorder patients and has been suggested as a hallmark of bipolar disorder. Indeed, some studies have shown that the levels of BDNF in the serum of bipolar disorder patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, bipolar disorder patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in bipolar disorder patients that may contribute to the pathophysiology of the disease.

Immediate early genes:

Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, and that includes stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity, the ability of brain cells to change in form and function in response to changes in the environment. Ultimately, it is the process of neuronal plasticity that gives the brain the ability to learn from and adapt to new experiences.

One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

[…]

in a previous study done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of bipolar disorder patients, suggesting that when facing a stressor, the EGR3 in bipolar disorder patients does not respond to the stimulus appropriately. Indeed, bipolar disorder patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. What the research group is now suggesting is that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in bipolar disorder, and that each of these two genes may affect each other’s expression in the cell. “We believe that the reduced level of BDNF that has been extensively observed in bipolar disorder patients is caused by the fact that EGR3 is repressed in the brain of bipolar disorder patients. The two molecules are interconnected in a regulatory pathway that is disrupted in bipolar disorder patients,”

Publication

Decreased exposure to air pollution associated with improved cognitive development and increases BDNF levels in children. www.sciencedaily.com

Brain Development Pollution BDNF

Exposure to air pollutants is associated with an increased risk of developing many health disorders, including heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and acute respiratory infections. Some evidence suggests that exposure to air pollution can impair neurological development in children. A 2014 study showed that reducing exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with improved cognitive development and increased BDNF levels in children.

Polycyclic aromatic hydrocarbons are produced during the combustion of coal, oil, gasoline, trash, tobacco, and wood. High-temperature cooking, such as grilling, promotes the formation of PAHs in meat and other foods. PAHs promote the formation of DNA adducts – covalent modifications of DNA that can drive carcinogenesis.

The study involved two cohorts of mother-child pairs who lived near a coal plant in China. One cohort of pairs was made up of 150 women who were pregnant while the coal power plant was operational and the other was made up of 158 women who were pregnant after it closed. None of the women smoked, and they all lived within 2.5 kilometers (about 1.5 miles) from the coal plant.

The authors of the study analyzed BDNF levels and their relationship to adduct formation and developmental outcomes in the two cohorts. They collected umbilical cord blood and maternal blood samples and measured the amount of DNA adducts in the samples. They also measured plasma levels of BDNF. When the children reached the age of two years, they underwent standardized testing that assessed motor, adaptive, language, and social development.

The children who were born to women who were pregnant after the plant closed had lower levels of PAH-DNA adducts, higher concentrations of BDNF, and higher developmental scores than those who were born to women who were pregnant when the plant was operational. Higher BDNF levels were associated with developmental scores. The findings suggest that reducing exposure to air pollutants during pregnancy lowers levels of PAH-DNA adducts and increases BDNF levels in infants.

Interestingly, clinical trials have demonstrated that sulforaphane, a compound derived from cruciferous vegetables (especially broccoli sprouts), can reduce the harmful effects of exposure to air pollutants (including PAHs) in humans. Sulforaphane works by switching on the activity of the body’s in-house detoxication pathways. Learn more about sulforaphane in this podcast featuring Dr. Jed Fahey.

Link to full study.

Women with a BDNF genetic variant experience fewer negative cognitive effects during chemotherapy. www.sciencedaily.com

Brain Cancer Dementia BDNF

Chemotherapy-associated cognitive impairment is a side-effect of chemotherapy in which people experience difficulties with concentration, decision making, and memory. Findings from a 2015 study suggest that women with a BDNF gene variation experience fewer cognitive problems during chemotherapy compared to those without this variation.

BDNF is a growth factor that is involved in the growth and repair of neurons. BDNF is expressed in the prefrontal cortex and hippocampus regions of the brain, which are involved in executive function, learning, and memory. A common variation in the BDNF gene called a single nucleotide polymorphism, or SNP, can alter how the BDNF protein functions. The SNP, known as Val66Met, results in the amino acid valine being replaced with methionine in the BDNF protein. Researchers have studied how the Val66Met SNP affects various aspects of cognition.

Previous research has demonstrated that women with breast cancer who were treated with chemotherapy experienced varying levels of cognitive decline. The current study investigated whether genetics, particularly variations in the BDNF gene, might make a person more susceptible to experiencing these effects.

The prospective cohort study involved 145 women (average age, 51 years) with early-stage breast cancer who were scheduled to receive chemotherapy. The authors of the study evaluated the participants' cognitive function using neuropsychological tools before, during, and at the end of chemotherapy treatment. Also, the researchers determined which version of the BDNF gene each participant possessed. If a patient’s test score during or at the end of treatment was 15 percent lower than baseline, they were considered to have cognitive impairment.

The authors observed that 54 women experienced cognitive impairment after treatment; however, those with the Met allele had fewer problems with verbal fluency and multitasking compared to those with the Val allele, particularly in older participants. This information may allow for early interventions in preventing cognitive impairment during chemotherapy.

These findings suggest that women may differ in their susceptibility to chemotherapy-associated cognitive impairment depending on which version of the BDNF gene they carry. Further research is required to confirm these findings, and brain imaging studies are needed to determine if these findings are the result of changes in brain anatomy.

Link to full study.

Restoration of BDNF-mediated signaling as a potential therapeutic strategy against Huntington's disease. www.sciencedaily.com

Brain BDNF Neurodegeneration

Huntington’s disease is a progressive neurodegenerative disorder characterized by uncontrolled movements, speech problems, personality changes, and dementia. The disease is caused by a single genetic mutation, called a CAG repeat, that drives abnormal protein folding and aggregation of the huntingtin protein and subsequent death of striatal neurons. Findings from a 2010 study demonstrate that modulating pathways involved in BDNF-mediated signaling shows promise as a therapeutic against Huntington’s disease.

Evidence suggests that normal huntingtin promotes the expression of BDNF, but mutated huntingtin impairs it. Striatal neurons need BDNF for their normal function and survival. A critical component in BDNF’s actions on striatal cells is a receptor called TrkB, to which BDNF binds. Levels of TrkB are diminished in Huntington’s disease.

The authors of the in vitro cell study investigated the effects of BDNF administration on mutant huntingtin. They found that altered cell-signaling in the Ras/MAPK/ERK1/2 pathway in cells expressing mutant huntingtin drove the loss of TrkB receptors, increased striatal cells' sensitivity to oxidative damage, and promoted cell death. These findings suggest that identifying ways to modulate the Ras/MAPK/ERK1/2 pathway and restore BDNF-related signaling shows promise as a therapeutic strategy against Huntington’s disease.

Link to full study.

BDNF genetic variant influences response to exposure therapy among people with PTSD. www.sciencedaily.com

Brain Behavior Anxiety BDNF

Exposure therapy is a type of cognitive behavioral therapy commonly used to treat people with posttraumatic stress disorder (PTSD). Some evidence suggests that BDNF mediates the response to exposure therapy, which can vary among people. A 2013 study demonstrated that genetic differences in BDNF expression influences how well a person responds to exposure therapy.

A single-nucleotide polymorphism (SNP) in the region of the DNA that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. Evidence suggests that carriers of the Met allele (Met/Met or Val/Met genotype) have reduced hippocampal function, poor episodic memory, and decreased exercise-induced secretion of BDNF.

The study involved 55 people between the ages of 18 and 65 years who had previously participated in an eight-week exposure therapy program. The participants provided DNA (via saliva samples) for BDNF genotyping.

The genotyping revealed that 30 participants carried the Val/Val BDNF allele, and 25 participants carried the Met-66 allele. Carriers of the Met-66 allele showed a poorer response to exposure therapy than carriers of the Val/Val allele, suggesting that the SNP influenced BDNF expression and subsequent response to cognitive behavioral therapy.

Link to full study.

Low BDNF during pregnancy is associated with depression during pregnancy and subsequent low fetal birth weight. www.sciencedaily.com

Brain Pregnancy Development BDNF

Depression is the most common form of mental health condition worldwide, affecting more than 322 million people. The disorder affects women disproportionately and is particularly common during pregnancy. Findings from a 2017 study demonstrated that serum levels of BDNF drop considerably during pregnancy, potentially increasing a woman’s risk for depression.

BDNF modulates synaptic plasticity and long-term potentiation – critical aspects of memory storage and brain function. Low BDNF levels are associated with increased risk for depression00181-1/fulltext?cc=y=).

The study involved 139 healthy pregnant women (77 Blacks and 62 whites) who were assessed three times during their pregnancies (once during each trimester) and again at four to 11 weeks postpartum. The authors of the study measured the participants' BDNF and cortisol levels via blood samples, gathered demographic data, and conducted psychosocial assessments. They reviewed the women’s medical records to determine their infants' birth weights.

The results of their assessments indicated that the women’s BDNF levels dropped considerably over the course of their pregnancies but rebounded during the postpartum period. In general, Black women had higher BDNF levels and lower cortisol levels than white women during pregnancy and postpartum. Lower levels of BDNF during the second and third trimesters were associated with higher risk for depression and lower birthweight babies, regardless of race.

Interestingly, these findings contradict those of an earlier study in rats and humans. However, the authors of the current study suggested that the conflicting findings may have been due to differences in assays used to measure BDNF.

Evidence indicates that exercise increases BDNF. Exercise is generally considered safe for pregnant women and may be a way to prevent some of the changes in mood that occur during pregnancy.

Preclinical evidence suggests BDNF may be a potent interventional tool in Alzheimer's and brain aging by directly improving learning and memory www.sciencedaily.com

Exercise Brain Alzheimer's Aging Memory BDNF

From the article:

For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer’s disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer’s disease.

[…]

“In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment.”

Brain-derived neurotrophic factor may be able to disrupt cocaine-seeking when applied directly to the nucleus accumbens in the brain [animal research] www.sciencedaily.com

Brain Behavior Addiction BDNF

From the article:

Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.

[…]

While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.

“An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”

The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.

BDNF from aerobic exercise may reduce loss of photoreceptor cells in macular degeneration: exercise reduced cell death by 50% in animal model www.sciencedaily.com

Aging Eyes Aerobic BDNF

From the article:

In the current study, the scientists trained mice to run on a treadmill for one hour per day, five days per week, for two weeks. After the animals were exposed to toxic bright light – a commonly used model of retinal degeneration – they exercised for two more weeks. The exercised animals lost only half the number of photoreceptor cells as animals that spent the equivalent amount of time on a stationary treadmill.

Additionally, the retinal cells of exercised mice were more responsive to light and had higher levels of a growth- and health-promoting protein called brain-derived neurotrophic factor (BDNF), which previous studies have linked to the beneficial effects of exercise. When the scientists blocked the receptors for BDNF in the exercised mice, they discovered that retinal function in the exercised mice was as poor as in the inactive mice, effectively eliminating the protective effects of the aerobic exercise.

Depressed or blocked BDNF activity has an interesting side-effect in rodents: increased aggression and social dominance seeking www.sciencedaily.com

Brain Behavior BDNF

From the article:

A/Prof. Je’s team generated transgenic mice in which the TrkB receptor was removed specifically in the GABAergic interneurons in the area of the brain regulating emotional and social behaviour, known as the corticolimbic system. The transgenic mice exhibited unusual aggressive behaviour when housed together with normal mice. To understand the origin of this behaviour, the team conducted behavioural tests. They found that the mice were not being aggressive to protect their territory. They were also not being aggressive because they were stronger; the transgenic mice were injured more than other mice during acts of aggression. Instead, their aggressive behaviour was a result of increased fighting for status and dominance over other mice in the group.

The researchers found that due to the loss of BDNF-TrkB, GABA-ergic interneurons in these transgenic mice supplied weaker inhibition to surrounding excitatory cells, which became overactive. They proceeded to shut down excitatory neurons in a specific area of the transgenic mice brains, which re-established the “excitatory/inhibitory” balance and which “instantaneously reversed the abnormal social dominance,” says Duke-NUS post-doctoral research fellow Dr. Shawn Pang Hao Tan, who was the first author of the paper.

BDNF response in obese subjects is better under in high-intensity conditions rather than moderate-intensity: addressing cognitive dysfunction in obese www.sciencedaily.com

Exercise Brain Obesity Aerobic BDNF Lactate

From the article:

Results of study, published in the journal Experimental Biology and Medicine, show that the BDNF response to acute high-intensity interval exercise was greater than continuous moderate-intensity exercise in obese subjects when compared to normal-weight subjects. Similarly, although acute high-intensity interval exercise induced greater blood lactate and plasma cortisol levels than continuous moderate-intensity exercise, obese subjects produced less blood lactate, but showed no difference in cortisol than normal-weight subjects.

These findings suggest that acute high-intensity interval exercise may be a more effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels.

Publication

Six weeks of 20-minute high-intensity interval training significantly improves "high-interference" memory, large fitness gains associated w/ more BDNF www.sciencedaily.com

Brain Performance Memory Aerobic BDNF

From the article:

Scientists have found that six weeks of intense exercise – short bouts of interval training over the course of 20 minutes – showed significant improvements in what is known as high-interference memory, which, for example, allows us to distinguish our car from another of the same make and model.

[…]

They also found that participants who experienced greater fitness gains also experienced greater increases in brain-derived neurotrophic factor (BDNF), a protein that supports the growth, function and survival of brain cells.

“Improvements in this type of memory from exercise might help to explain the previously established link between aerobic exercise and better academic performance,” says Jennifer Heisz, an assistant professor in the Department of Kinesiology at McMaster and lead author of the study.

Brain-derived neurotrophic factor levels reveal overall severity of traumatic brain injuries -- sharp reductions in TBI after injury predict outcomes www.sciencedaily.com

Brain BDNF

From the article:

Korley and collaborators around the country wanted to know if a blood test could better predict which patients would have ongoing brain injury-related problems, to provide better treatment for them. So they measured the levels of three proteins that they suspected play a role in brain cell activity in more than 300 patients with a TBI and 150 patients without brain injuries. Then, they followed those with a TBI for the next six months.

Levels of one protein, called brain-derived neurotrophic factor (BDNF), taken within 24 hours of someone’s head injury, could predict the severity of a TBI and how a patient would fare, they found. While healthy people averaged 60 nanograms per milliliter of BDNF in their bloodstreams, patients with brain injuries had less than one-third of that amount, averaging less than 20 nanograms per milliliter, and those with the most severe TBIs had even lower levels, around 4 nanograms per milliliter. Moreover, patients with high levels of BDNF had mostly recovered from their injuries six months later. But in patients with the lowest levels of BDNF, symptoms still lingered at follow-up. The results suggest that a test for BDNF levels, administered in the emergency room, could help stratify patients.

Publication

Every other day fasting in mice protected brain from neurotoxic injury, prior work showing enhanced BDNF www.sciencedaily.com

Brain Fasting BDNF

From the article:

Mice on these three diets were given a neurotoxin called kainate, which damages nerve cells in a brain region called the hippocampus that is critical for learning and memory. (In humans, nerve cells in the hippocampus are destroyed by Alzheimer’s disease). Dr. Mattson’s team found that nerve cells of the meal-skipping mice were more resistant to neurotoxin injury or death than nerve cells of the mice on either of the other diets.

[…]

Previous studies by Dr. Mattson and his colleagues suggested that nerve cells in the brains of rodents on a meal-skipping diet are more resistant to dysfunction and death in experimental models of stroke and other neurological disorders including Parkinson’s, Alzheimer’s and Huntington’s diseases. Dr. Mattson also has found that meal-skipping diets can stimulate brain cells in mice to produce a protein called brain-derived neurotrophic factor (BDNF) that promotes the survival and growth of nerve cells.

Publication

Beta-hydroxybutyrate, a ketone, increases brain-derived neurotrophic factor expression: relevance for neurodegenerative disease www.sciencedaily.com

Exercise Brain Alzheimer's Diet Ketosis BDNF HDAC Inhibitor

β-hydroxybutyrate production consequent to exercise induces within the muscle the activities of a key promoter involved in the production of brain-derived neurotrophic factor.

From the article:

Studies have shown that BDNF levels in the brains of people with Alzheimer’s or Huntington’s disease are, on average, half that of people without either brain-damaging disease.

Among the key findings of the current study was that a ketone, a chemical naturally produced in the liver called beta-hydroxybutyrate (DBHB), triggers biological reactions that activate the BDNF gene to produce more of its protein. DBHB has long been known to build up in the body and brain with exercise. Ketones are “by-product” chemicals made when animals break down fat as an alternative energy source after having drained more readily available sugar stores during exercise.

Specifically, Chao says, the researchers found that DBHB prevents other proteins in the brain known as histone deacetylase complexes, or HDACs, from suppressing BDNF production by altering the environment of the BDNF gene.

Publication

Brain Obesity Memory Fat BDNF Thermogenesis

From the article:

“Up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food.”

[…]

The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water.

Key findings include the following:

• Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).

• Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.

• Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.

Increases in brain-derived neurotrophic factor from aerobic exercise associated with appetite suppression, weight loss, and improved blood pressure www.sciencedaily.com

Exercise Brain Obesity Blood Pressure Aerobic Weight Loss BDNF

From the article:

The team evaluated blood levels of BDNF before and after a three-month program of aerobic exercise in 15 overweight or obese men and women. The seven men and eight women, ages 26 to 51, worked out on a treadmill and bicycle. They were asked about their calorie intake and told to continue eating their usual number of calories. The participants were unaware that one of the study’s objectives was to evaluate changes in food intake.

At the end of the study, the subjects had decreased BMI, waist circumference, and blood pressure, the data showed. They also reported consuming fewer calories than at the beginning of the study. Over the three months, BDNF levels greatly increased. This higher the concentration of BDNF, the less the subject’s intake of calories and the greater the weight loss, Araya said.

Thus, it is possible that increases in BDNF suppress appetite, she said. They did not test appetite suppression directly, but some past studies have shown that aerobic exercise suppresses appetite.

Greater BDNF expression in brain tied to up to 50% slower decline in memory in older people (for those in top decile of expression) www.sciencedaily.com

Brain Alzheimer's Memory Dementia BDNF

A study of BDNF gene expression in post-mortem brain tissue found that BDNF may provide a buffer against dementia, particularly when higher expression is found in the context of the classical Alzheimer’s brain pathology of amyloid-beta plaques and tau tangles.

From the article:

For the study, 535 people with an average age of 81 were followed until death, for an average of six years. They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems. Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured.

[…]

The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent. The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

Brain-derived neurotrophic factor (BDNF) featured article

Episodes

How Micronutrients & Exercise Ameliorate Aging | Dr. Rhonda Patrick

Why vigorous exercise improves cognitive function | Dr. Martin Gibala

Topic Pages

News & Publications