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Light-based therapy enhances recovery after spinal cord injury in rats by reducing tissue scarring and promoting nerve cell regeneration. medicalxpress.com
More than 900,000 people worldwide experience a spinal cord injury each year, primarily due to falls and motor vehicle accidents. These injuries often cause lifelong physical debilities, impairing mobility and reducing quality of life. A recent study in rats found that photobiomodulation (light-based therapy) enhanced recovery after a spinal cord injury.
Researchers investigated two light-based therapy methods using a rat model of spinal cord injury. One method used transcutaneous (through the skin) red-light or laser-light treatment, while the other used an implantable device.
The researchers found that both delivery methods produced comparable outcomes, with a daily one-minute dose of 660-nanometer light for seven days reducing tissue scarring at the injury site and enhancing functional recovery. They also noted increased levels of proteins associated with nerve cell regeneration and improved connectivity between cells in the injured spinal areas.
These findings suggest that photobiomodulation enhances recovery after spinal injury in rats and holds potential for future therapeutic applications in humans.
Photobiomodulation employs specific wavelengths of light to stimulate biological processes within cells and tissues, triggering a cascade of physiological responses. Evidence suggests photobiomodulation has potential applications in medicine, dentistry, cosmetic procedures, and scientific research. Learn more about photobiomodulation in our overview article.
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Estrogen may improve memory and promote neuron repair and function, while progesterone alone may adversely affect memory, rodent studies suggest(2004) www.sciencedaily.com
From the article:
Cyclic administration of estrogen might be inferior to continuous or no administration in terms of improving memory functions.
Researchers removed the ovaries of 32 middle-aged mice before starting them on various courses of HT lasting three months. A continuous group received estrogen injections daily, a cyclical group was administered estrogen every four days, and a control group received daily injections with no estrogen.
After three months, the mice underwent a variety of cognitive tests. […] Mice were tested every day for two weeks for both spatial reference memory (long-term memory for information that did not change during the test session) and working memory (short-term memory for information that changed in each trial).
Mice on the cyclical regimen made more reference and working memory errors than control mice. The cyclical group also made more reference memory errors than mice receiving continuous estrogen.
Another test focused on object recognition, a type of nonspatial memory. […] Because mice have a natural tendency to explore novel objects, mice with good memory for the original objects should spend more time examining the new object. Again, mice in the control and continuous groups outperformed the cyclical HT mice.
Estrogen may promote neuron repair and improve neuronal function.
Other researchers studied the effects of continuous versus no administration of HT. Investigators removed the ovaries of mice aged 8 to 12 weeks and either treated them with continuous estrogen for 47 days or did not treat them with estrogen. Researchers then sacrificed the mice at different time periods after estrogen exposure (at 5, 14, 28, and 47 day intervals) and examined them for the production of the proteins associated with neuron repair and the formation of contacts between neurons.
[…]
After five days on estrogen, the estrogen-treated mice produced more of the proteins important for repair and neuronal function. However, with prolonged, continuous estrogen treatment, this effect diminished, and by day 47 the estrogen-treated mice were similar to the non-estrogen-treated mice in levels of the repair proteins. In addition, at the end of the experiment, mice that did not receive estrogen showed an elevation of a brain protein associated with the negative aspects of brain aging, while estrogen-treated mice did not.
Progesterone may be detrimental to learning and increase short-term memory deficits in aged rats.
Thirty rats were used in the study. Ten rats kept their ovaries, and twenty rats had their ovaries removed. The ovariectomized rats were then divided into two groups: those receiving progesterone and a control group that did not receive progesterone.
As in the Yale study, a water maze was used to test working and reference memory. The maze difficulty was changed at increasing rates, forcing the rats to remember greater amounts of information. The rats receiving progesterone exhibited deficiencies in learning and remembering the maze. In addition, rats treated with progesterone also showed problems remembering many items of information, while untreated rats were able to successfully remember the items.
Progesterone may inhibit neuroprotective effects of estrogen
In the first experiment, levels of beta-amyloid protein were evaluated after a six-week period of hormone treatment. Higher levels of beta-amyloid protein were observed in the hormone-depleted rats compared with control animals. The group receiving estrogen did not experience an increase in levels of beta-amyloid. For the rats receiving the combination of estrogen and progesterone, although progesterone failed to decrease beta-amyloid levels, it did not alter the ability of the estrogen treatment to reduce beta-amyloid levels.
In the second study, rats were treated with a mild dose of neurotoxin after two weeks of hormone treatment. The hormone-depleted rats experienced the greatest amount of neuronal death. In estrogen-treated rats a protective effective against neuronal death was observed, while rats treated with estrogen and progesterone in combination did exhibit neuronal death, suggesting that progesterone inhibited the neuroprotective action of estrogen in this model.
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Estradiol may heighten the sensitivity of sound-processing neurons and activate genes that instruct the brain to lay down memories of sounds. (2009) www.sciencedaily.com
From the article:
Previous studies have hinted at a connection between estrogen and hearing in women who have low estrogen, such as often occurs after menopause, says Pinaud. No one understood, however, that estrogen was playing such a direct role in determining auditory functions in the brain, he says. “Now it is clear that estrogen is a key molecule carrying brain signals, and that the right balance of hormone levels in men and women is important for reasons beyond its role as a sex hormone,” says Pinaud.
Pinaud, along with Liisa Tremere, a research assistant professor of brain and cognitive sciences, and Jin Jeong, a postdoctoral fellow in Pinaud’s laboratory, demonstrated that increasing estrogen levels in brain regions that process auditory information caused heightened sensitivity of sound-processing neurons, which encoded more complex and subtle features of the sound stimulus. Perhaps more surprising, says Pinaud, is that by blocking either the actions of estrogen directly, or preventing brain cells from producing estrogen within auditory centers, the signaling that is necessary for the brain to process sounds essentially shuts down. Pinaud’s team also shows that estrogen is required to activate genes that instruct the brain to lay down memories of those sounds.
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Elevated testosterone induces apoptosis in neuronal cells, cell study suggests. (2006) www.sciencedaily.com
From the article:
The researchers showed that high levels of testosterone triggered programmed cell death in nerve cells in culture. Cell death, or apoptosis, is critical in many life processes, including development and disease. It is characterized by membrane instability, activation of caspases, which are the executioner proteins in apoptosis, change in membrane potential, and DNA fragmentation.
“In the present study we have demonstrated for the first time that the treatment of neuroblastoma cells with elevated concentrations of testosterone for relatively short periods, six to 12 hours, induces a decrease in cell viability by activation of a cell death program,” Ehrlich said. “Low concentrations of testosterone had no effects on cell viability, whereas at high concentrations the cell viability decreased with incremental increases in hormone concentration.”
The testosterone-induced apoptosis described in this study occurs through overactivation of intracellular Ca2+ signaling pathways. Overstimulation of the apoptotic program in neurons has been associated with several neurological illnesses, such as Alzheimer disease and Huntington disease.
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Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in models of Parkinson’s disease. (2006) www.sciencedaily.com
Blocking the action of TNF-alpha may slow the progression of Parkinson’s disease.
Parkinson’s disease is a progressive neurodegenerative disorder that affects the central nervous system. It is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. Approximately 1 percent of all adults over the age of 60 years lives with Parkinson’s disease. Findings from a 2006 study suggest that blocking the action of tumor necrosis factor-alpha slows the progression of Parkinson’s disease.
Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders, including cancer, autoimmune diseases, Alzheimer’s disease, and depression.
The investigators injected the brains of mice with either lipopolysaccharide (LPS, an endotoxin that promotes acute inflammation) or 6-hydroxydopamine (a neurotoxin) and assessed the animals' brains for evidence of substantia nigra cell death. They injected a compound called XENP345 (a TNF-alpha inhibitor) into the brains of some of the mice. They also applied LPS and 6-hydroxydopamine to cultured neuronal cells and assessed the effects of XENP345 on cell death.
They found that both LPS and 6-hydroxydopamine caused marked cell death in the substantia nigra region of the animals' brains. They also found that inhibiting TNF-alpha via XENP345 in the brains and in cultured cells reduced cell death by roughly half.
These findings suggest that inhibiting the activity of the pro-inflammatory cytokine TNF-alpha reduces cell death in an animal model of Parkinson’s disease. Robust evidence indicates that exercise, which also reduces inflammation, slows the progression of Parkinson’s disease. Learn more about the effects of exercise on Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Interleukin-6 (IL-6) may have a neuroprotective function, mouse study suggests. (2003) www.sciencedaily.com
From the article:
One of the biggest challenges we face as a society is the eventual loss and degeneration of neurons from many causes, including many diseases – from Alzheimer’s disease to multiple sclerosis to Parkinson’s disease – and other sorts of injury.
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To function in a cell, IL-6 has to bind in a specific place – called a “receptor site” – in a specific way. Dr. Rodriguez and colleagues were intrigued that IL-6 uses the same receptor site used by compounds whose job is to promote neuronal survival. “To me, that was pretty wild,” Dr. Rodriguez says. “So I hypothesized that maybe this IL-6 is also playing a role in protecting neurons.”
Testing this idea required extensive genetic work to produce different mouse groups that varied in their ability to produce IL-6. All were infected with a virus that causes a degenerative nerve disease. Animals with the IL-6 gene got mildly sick, but did not die. Mice lacking the IL-6 gene got severely sick and started dying. Why?
To find a cause of death, the Mayo Clinic team analyzed the animals' tissues. Their findings: neurons in the spinal cords of mice lacking IL-6 were degenerating dramatically. This evidence supported their hypothesis of a neuron-protection role for IL-6. It also led them to their next question: Where is IL-6 made?
An analysis of the brains of healthy mice possessing the IL-6 gene surprised them. “You look for IL-6 in the brain of a normal, healthy animal, and there is no IL-6 in a normal healthy animal!” Dr. Rodriguez says. “So then we infected the animals with the virus. Now when we looked for IL-6, guess what? It was everywhere.”
Specifically, IL-6 was found in astrocytes.
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Excess visceral fat promotes inflammation and drives cognitive decline. www.eurekalert.org
Visceral fat – body fat that is stored in the abdominal cavity in close proximity to important internal organs such as the liver, pancreas, and intestines – plays a central role in the interrelationship between obesity and systemic inflammation. Excess visceral fat, often referred to as central or abdominal obesity, is a strong predictor of age-related cognitive decline. A new study in mice demonstrates that having excess visceral fat may impair cognition by activating the NLRP3 inflammasome and promoting the release of interleukin-1 beta (IL-1β).
Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. Cryopyrin, also known as NLRP3, is a protein that drives the formation and activation of the NLRP3 inflammasome.
Interleukin-1 beta is a proinflammatory protein present in many cells. NLRP3 inflammasome-driven release of IL-1β activates microglia, the brain’s resident immune cells. Microglia serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and harm.
The authors of the study first determined that mice lacking the gene for NLRP3 did not experience visceral fat-induced brain inflammation and cognitive decline. They also determined that when visceral fat from normal, obese mice was transplanted into these mice, they exhibited higher levels of IL-1β in their hippocampus, an area of the brain associated with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation.
To understand the effects of IL-1β on brain function, the authors of the study fed the mice a high- or low-fat diet for 12 weeks and then assessed the animals' capacity to navigate a water maze. The mice that ate the higher-fat diet experienced greater difficulties negotiating the water maze, compared to those that ate the lower-fat diet. Examination of the animals' brains revealed that the mice that ate the high-fat diet (as well as those that received the fat transplants) had weaker synapses between the neurons involved in learning and memory.
These findings suggest that chronic inflammation driven by excess visceral fat may contribute to cognitive decline by promoting the release of IL-1β and increasing inflammation. Inflammation drives other aspects of brain dysfunction, including those associated with depression. Watch this clip in which Dr. Charles Raison discusses how a pro-inflammatory environment can contribute to the risk of depression.
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As many as 10 million people living in the United States have low iron levels. Findings from a new study suggest that iron levels in the basal ganglia region of the brain during youth influence cognitive ability.
Iron is an essential nutrient that plays critical roles in many facets of brain function, including cellular respiration, neurotransmitter synthesis, and myelination – a process essential to nerve cell transmission and cognitive development. Iron can be obtained in the diet from both animal and plant sources.
The basal ganglia comprise clusters of neurons located deep within the cerebral hemispheres, at the base of the forebrain and the top of the midbrain. They participate in a wide range of cognitive, motor, and emotive functions.
The longitudinal study involved more than 800 young people between the ages of 8 and 26 years old who were enrolled in the Philadelphia Neurodevelopment Cohort study. The participants underwent neuroimaging scans up to three times during the study period to quantify iron levels in four regions (caudate, putamen, nucleus accumbens, and globus pallidus) of their basal ganglia. They also completed cognitive performance tests to assess executive control, complex cognition, episodic memory, social cognition, and motor speed.
The imaging scans revealed that iron levels increased over time in all four regions of the basal ganglia, with the greatest concentrations present in the globus pallidus and putamen, areas that regulate voluntary movement and learning. Higher iron concentrations in the putamen, in particular, were related to higher cognitive abilities among the participants. The accumulation of iron in these regions occurred earlier in females.
These findings highlight the importance of proper nutrition during development and suggest that iron supplementation may be beneficial, especially during adolescence.
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Children of women exposed to parabens during pregnancy are at greater risk of being obese. www.sciencedaily.com
Obesity is a growing problem worldwide, especially among children and young adults. Many factors contribute to obesity, including environmental exposures, which can drive epigenetic changes. Findings from a new study suggest that maternal exposure to parabens may increase the risk of obesity among children.
Parabens are widely used synthetic compounds that exert antibacterial and antifungal properties. They are commonly used in cosmetics, drugs, and some foods. Parabens can be ingested or absorbed through the skin. Some evidence suggests that parabens are endocrine disruptors.
The study had multiple arms that included an analysis of epidemiological data from the German LINA study and an experimental study in mice that simulated paraben exposure during pregnancy. The epidemiological data revealed that the children of women who had high exposure to parabens during pregnancy (assessed by urinary excretion) were more likely to be obese, an effect that was more pronounced in girls. Findings from the mouse study suggested that this increased risk of obesity was driven by epigenetic mechanisms associated with the altered expression of the proopiomelanocortin gene (known as POMC), which plays critical roles in the neuronal regulation of appetite, satiety, and food intake.
These findings suggest that prenatal environmental exposures to everyday compounds such as parabens may have far-reaching effects on the health of offspring.
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As we age, our ability to learn things and form new memories decreases. Navigation, which incorporates multiple cognitive processes including memory, attention, and our perception of direction and distance, becomes particularly difficult with aging. Findings from a recent study suggest that increasing adult neurogenesis may improve navigation capacity in older mice.
Neurogenesis is the process of forming new neurons. It is essential during embryonic development, but also continues in certain brain regions throughout human lifespan to facilitate learning and memory formation.
The study authors increased the expression of Cdk4/cyclinD1, a multi-protein complex that governs the cell cycle and its progression, in neural stem and progenitor cells (NSC) to enhance both their cell cycle activity and proliferation in mice. This increased neurogenesis in the animals' brains and improved their ability to perform navigation skills.
These findings suggest that age-related cognitive impairments may be reversed in old age by tapping into the brain’s neurogenic processes.
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Stress has far-reaching effects on the human body, including increased risk of chronic disease and other conditions associated with aging. Anecdotal reports suggest that stress can contribute to the premature graying of hair. Findings from a recent study in mice suggest that acute stress depletes melanocyte stem cell populations to promote the graying of hair.
Melanocyte stem cells are undifferentiated cells found in the region of hair associated with growth. They give rise to melanocytes, the mature, melanin-forming cells that provide color to growing hair.
Both mental and physical stress activate the body’s sympathetic nervous system, one of the two main divisions of the autonomic nervous system (the other being the parasympathetic nervous system). The sympathetic nervous system’s primary purpose is to stimulate the body’s fight-or-flight response to stress. A critical element in this response is noradrenaline, a type of hormone and neurotransmitter that plays a role in vigilance and conditioned fear.
The authors of the study induced acute stress in mice and noted that the mice exhibited increased numbers of gray hairs. This increased graying was attributed to the activation of sympathetic nerves in the region in which the stem cells reside and subsequent release of noradrenaline, which promoted stem cell proliferation, differentiation, migration, and eventual depletion.
These findings suggest that neuronal activity induced by an acute stressor can drive stem cell loss and illustrate how overall mental and physical health influence stem cell health.
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One night of sleep deprivation in healthy young men caused increased blood levels of tau, a protein that forms tangles in the brain. www.eurekalert.org
Sleep disruption is intrinsically linked with Alzheimer’s disease and its pathophysiology, with characteristic changes in sleep emerging early in life, well before the clinical onset of the disease. A key player in the development of Alzheimer’s disease is amyloid-beta. Insufficient sleep increases the production of amyloid-beta, and amyloid-beta deposition, in turn, impairs sleep in a vicious, self-perpetuating loop. Findings from a new study demonstrate that sleep deprivation also increases blood levels of tau, a protein found in the brain.
Tau is a microtubule-bound protein that forms the neurofibrillary “tau tangles” associated with Alzheimer’s disease. Tau tangles disrupt the transport of metabolites, lipids, and mitochondria across a neuron to the synapse where neurotransmission occurs. Diminished slow-wave sleep is associated with higher levels of tau in the brain. Elevated tau is a sign of Alzheimer’s disease and has been linked to cognitive decline.
The two-condition crossover study involved 15 healthy young men who were randomized to regimens of either two nights of consecutive sleep or one night of sleep followed by one night of sleep deprivation. Following the one night of sleep deprivation, participants' blood levels of tau increased approximately 17 percent, compared to an approximately 2 percent increase following the night of sleep. Other biomarkers of Alzheimer’s disease-associated proteins were unchanged. While tau tangle formation in neurons can disrupt normal function, it is unclear what elevated blood levels of tau protein mean. Future studies are needed to elucidate this finding.
Watch this clip featuring Dr. Matthew Walker in which he describes current research focused on identifying age-related sleep deprivation vulnerability windows for prevention of Alzheimer’s disease.
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Higher physical activity halves risk of depression in a large study of more than 395,000 adults. www.sciencedirect.com
Exercise and other forms of physical activity elicit a wide range of beneficial health effects. Findings from a large study in Sweden suggest that physical activity reduces the risk of depression.
The observational study involved more than 395,000 people who were followed over a period of 21 years. The study participants were either skiers who partook in Vasaloppet, an annual long-distance cross-country ski race held annually in Sweden (physically active), or non-skiers (physically inactive). Vasaloppet skiers typically exercise a minimum of four hours weekly and have a high level of physical fitness.
The findings indicated that physical activity was associated with a 50 percent lower risk of developing depression during a 10-year period compared to physical inactivity. Adjustments for age, sex, and education did not alter the results.
Some have suggested that the association between higher level of physical activity and lower risk of depression might be an artifact of reverse causation. For example, people with depression – especially those whose condition is undiagnosed – might be less likely to engage in physical activity. However, Mendelian randomization studies and data from molecular, genetic, and interventional trials suggests that the relationship is indeed causal.
Check out our in-depth video covering exercise and depression, including data from randomized controlled trials, Mendelian randomization trials, mechanistic studies, and even ideal exercise parameters.
An easy take-home message: Aerobic exercise at 70 to 80 percent of maximum heart rate for 40 minutes or more may be critical for boosting brain-derived neurotrophic factor (BDNF) – a growth factor that controls and promotes the growth of new neurons.
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Higher cardiorespiratory fitness associated with increases in gray matter volume. newsnetwork.mayoclinic.org
Cardiorespiratory fitness is a measure of the body’s ability to deliver oxygen to skeletal muscles during sustained physical activity. Findings from a new study suggest that higher cardiorespiratory fitness may increase the brain’s gray matter.
Gray matter contains the cell bodies, dendrites, and axon terminals of neurons in the brain. Loss of gray matter is associated with cognitive decline and memory loss – hallmarks of dementia. Physical inactivity promotes gray matter losses and is a major risk factor for dementia.
The new study involved more than 2,100 adults between the ages of 21 and 84 years living in Germany. The authors of the study assessed the participants' cardiorespiratory fitness based on peak oxygen uptake during exercise on a stationary bike. They also measured the participants' gray matter and total brain volume using magnetic resonance imaging (MRI).
The MRI analysis revealed that for a single standard deviation increase in peak oxygen uptake, gray matter volume increased by more than 5 cubic centimeters in regions associated with emotion, memory encoding, learning, and decision making. These findings suggest that physical activity that promotes cardiorespiratory fitness might be a means to prevent dementia associated with gray matter losses.
Sauna bathing is an exercise mimetic and promotes many of the cardiovascular benefits associated with exercise. Dr. Rhonda Patrick describes some of these effects in this podcast.
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Increasing gamma rhythm activity in the brain can affect the pathology and symptoms of Alzheimer’s disease picower.mit.edu
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. The primary pathological hallmarks of Alzheimer’s disease include amyloid-beta plaques and tau tangles. Abnormal electrical activity in the brain can worsen the condition. A recent review describes findings from two rodent studies suggesting that stimulating gamma waves in the brain may reverse the pathology and symptoms of Alzheimer’s disease.
During wakefulness and periods of REM sleep, the human brain exhibits spontaneous rhythmical activity in the form of fast-moving gamma waves. These waves are evoked by intense attention, conditioned responses, tasks requiring fine movements, or sensory stimuli.
The studies utilized mice that were predisposed to Alzheimer’s disease. These mice often exhibit diminished gamma wave activity. The authors of the studies exposed the mice to visual and auditory stimuli that were designed to promote gamma wave activity.
Following exposure to visual stimuli alone, the mice exhibited reduced amyloid burden and structural changes in the microglial cells in the visual cortex of their brains. These structural changes were consistent with increased phagocytic capacity, which is crucial for the clearance of apoptotic or necrotic cells and the removal of amyloid-beta. Exposure to auditory stimuli alone had similar effects on microglial activity and amyloid burden in the auditory cortex of the mice’s brains, but the mice also exhibited improved performance on several hippocampal-dependent tasks and improved brain vasculature.
When the mice were exposed to combined auditory and visual stimuli to promote gamma wave activity, the amyloid burden was reduced throughout the neocortex, the area of the brain that processes sensory, motor, language, emotional, and associative information. In addition, the microglia in several regions of the brain exhibited a clustering pattern around the amyloid plaques that facilitated clearance.
These findings suggest that non-invasive techniques that promote gamma wave activity in the brain may be useful in treating people with Alzheimer’s disease.
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Gut bacteria may alter the aging process of the human brain through the production of butyrate www.sciencedaily.com
The gut microbiota is a complex and dynamic population of microorganisms that is subject to change throughout an individual’s lifespan in response to the aging process. Findings from a new study demonstrate that altering the gut microbial population may alter the aging process of the human brain.
The authors of the study transplanted gut microbiota samples from healthy young or old mice into young germ-free mice. Eight weeks after the transplant, the mice that received microbial samples from the old mice demonstrated increased neurogenesis – the process of forming new neurons – in the hippocampus region of their brains.
Further analysis revealed that these mice also had larger numbers of butyrate-producing microbes in their colons. Butyrate, a short-chain fatty acid, is produced during bacterial fermentation in the human colon and has wide-ranging effects on human physiology. In this study, butyrate was associated with an increase in growth factors and subsequent activation of key longevity signaling pathways in the livers of the recipient mice. When butyrate alone was given to the recipient mice it promoted neurogenesis, as well.
The findings from this study may have relevance for dietary interventions to maintain or improve brain health.
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Waves of Fluid Bathe the Sleeping Brain, Perhaps to Clear Waste www.the-scientist.com
The glymphatic system – a vast arrangement of cerebrospinal fluid-filled cavities surrounding the small blood vessels in the brain – facilitates the removal of proteins and metabolites from the central nervous system. During sleep, these interstitial spaces increase by more than 60 percent. A new study demonstrates that large quantities of cerebrospinal fluid flow through these spaces in a rhythmic fashion during deep sleep to remove waste.
The study involved 13 young, healthy men and women whose neuronal activity, blood levels, and cerebrospinal fluid (CSF) flow were measured during sleep. As the study subjects slept, a large wave of CSF flowed through their brains roughly every 20 seconds, preceded by changes in brain neuronal activity and blood flow.
Poor sleep – which would impair glymphatic function – has been linked to a variety of neurodegenerative diseases. For example, disruption in deep sleep is highly pronounced in people with Alzheimer’s disease and typically precedes diagnosis.
Glymphatic activation has also been shown to play a key role in the transport of biomarkers of traumatic brain injury (TBI). In particular, cerebrospinal fluid-mediated removal of tau protein in the brain via glymphatic routes is crucial for limiting secondary neuronal damage following traumatic brain injury. Unfortunately, some types of TBI impair glymphatic function and may be one reason why people with TBI are at a higher risk for neurodegenerative diseases.
Taken together, these data suggest that sleep – especially deep sleep – is not only important for the prevention of Alzheimer’s disease but also may be key in the treatment of TBI.
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THC given to old mice improved performance on memory tests. www.scientificamerican.com
THC (found in cannabis) that was given to old mice improved performance on learning and memory tests, improved connections between neurons, and resulted in gene activation profiles in the hippocampus that resembled young mice.
The mice that were 12 months old (mature mice) and 18 months old (old mice) both performed better after given THC and this on was dependant on activation of glutamatergic CB1 receptors and histone acetylation that was induced by THC.
In contrast, young mice given THC performed worse on memory tests. The mice termed “young” in this study were 2 months old. They performed worse on memory tests after given THC. Typically a mouse is termed “adult” if it is 3 months old. It seems possible that some brain development may still occur at 2 months of age but I’m not sure.
It is unclear whether THC will improve memory in older adults but this preclinical study provides strong evidence along with a mechanism that it might.
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A 28% lower risk of dementia and better cognition was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men. www.sciencedaily.com
A 28% lower risk of dementia and better scores on tests for memory and linguistic abilities was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men.
Choline is an important precursor to the neurotransmitter acetylcholine which plays an important role in cognition. Phosphatidylcholine is a very important component of cell membranes that make up neurons and also combines with the omega-3 fatty acid DHA to form lysophosphatidylcholine DHA which is transported across the blood-brain barrier. I published a paper last year on the important role DHA in phosphatidylcholine form plays in preventing Alzheimer’s disease particularly in people genetically predisposed to the disease.
This new study was an observational study so causation cannot be established. Future clinical trials need to be done before definitive conclusions can be made.
Link to my study on DHA and Alzheimer’s disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338661/
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Stem cells derived from placenta were able to regenerate healthy heart cells after heart attacks in animals. www.eurekalert.org
Stem cells derived from placenta were able to regenerate healthy heart cells after heart attacks in animals. The placental stem cells traveled to the site of the injury in the heart and formed beating heart cells that helped repair damage.
To learn more about stem cells derived from placenta, check out the podcast I did a few years ago with Dr. Frans Kuyper who discovered how the human placenta is a rich source of pluripotent stem cells and yet the placenta is thrown away after delivery. We discuss how his lab has shown that the stem cells from the placenta can be transformed into neuron-like cells, fat cells, bone cells, endothelial cells (relevant for lung and blood vessels), and liver cells. His lab also developed a technique for harvesting 5 to 7 times more hematopoietic stem cells from placenta than is currently retrieved from cord blood, a more standard, established source that is used worldwide for a bone-marrow transplant.
There are a couple of companies that bank placenta and cord blood after your baby is born. I chose to bank both placenta and cord blood after the birth of my son. I decided to go with Life Bank USA (no affiliation) to bank my cord blood and placenta because I really liked the research they are doing with placental stem cells. I hope to see more well-established cord blood companies start banking placental tissue…it is so worth it.
Foundmyfitness placental stem cell episode: https://www.foundmyfitness.com/episodes/frans-kuypers
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A new study shows that even 80-year-olds can grow new neurons in the hippocampus region of the brain, but this process is decreased in people with AD. www.the-scientist.com
A new study shows that even 80-year-olds can grow new neurons in the hippocampus region of the brain, but this process is decreased in people with Alzheimer’s disease.
The process of growing new neurons is called neurogenesis and it is highly active during brain development but whether it occurs in adults has been unclear. An animal study published last year had shed some doubt on adult neurogenesis claiming it does not occur.
A new study using cutting-edge techniques looked at human samples and provided pretty solid evidence of neurogenesis in adult humans. It also found that in tissue samples from people with Alzheimer’s disease, neurogenesis was dramatically diminished. This is in line with brain imaging studies showing brain atrophy in the hippocampus brain region in Alzheimer’s disease patients.
One of the major regulators of neurogenesis is the growth factor BDNF. Studies have shown 30 minutes of exercise can increase BDNF in humans. BDNF is able to cross the blood-brain barrier and promote the growth of new neurons.
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People with Parkinson's disease that received a growth factor (GDNF) experienced a 100% improvement in dopamine uptake in a key brain region. sciencesources.eurekalert.org
People with Parkinson’s disease that received a growth factor (GDNF) experienced a 100% improvement in dopamine uptake in a key brain region involved in the disease compared to the placebo group which did not experience any change. The participants that received GDNF also showed moderate to large improvements in symptoms.
The GDNF was implanted into the brain using robot-assisted neurosurgery. This delivery system allowed a high flow rate of GDNF infusions that were administered every four weeks.
Parkinson’s disease leads to a substantial decrease in dopamine-producing neurons in the brain. These neurons are important for motor control and other cognitive functions.
Several animal studies have identified GDNF as an important regulator of dopamine neurons in the brain. Interestingly, animal studies have also shown that GDNF is produced in the brain after acute and long-term exercise. Exercise has been shown to improve Parkinson’s disease symptoms in several clinical trials.
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A single dose of psilocybin enhanced creative thinking, empathy, and subjective well-being in participants for up to seven days after use. www.tandfonline.com
A new study finds that a single dose of psilocybin enhanced creative thinking, empathy, and subjective well-being in participants for up to seven days after use.
There have been multiple studies that have now found psilocybin appears to have a positive effect on well-being and improve symptoms of depression possibly through its effects on the serotonin receptor. Animal studies have shown that psilocybin increases neurogenesis which is the growth of new neurons in certain brain regions. Interestingly, serotonin is also linked to neurogenesis.
I’m no expert in this field but I did interview the expert on psilocybin, Dr. Roland Griffiths. He has conducted several controlled trials on psilocybin ranging from its effects on depression to addiction. He talks in depth about how this compound can have varying effects based on dose.
If you are interested in learning more about this research check out the episode with Dr. Griffiths.
Episode: https://www.foundmyfitness.com/episodes/roland-griffiths
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Betaine reduces β-amyloid-induced paralysis in an Alzheimer model of Caenorhabditis elegans | Genes & Nutrition | Full Text genesandnutrition.biomedcentral.com
Full Title: Betaine reduces β-amyloid-induced paralysis through activation of cystathionine-β-synthase in an Alzheimer model of Caenorhabditis elegans
Betaine at a concentration of 100 μM was able to reduce homocysteine levels in the presence and absence of 1 mM homocysteine. Simultaneously, betaine both reduced normal paralysis rates in the absence of homocysteine and increased paralysis rates triggered by addition of homocysteine. Knockdown of cystathionine-β-synthase using RNA interference both increased homocysteine levels and paralysis. Additionally, it prevented the reducing effects of betaine on homocysteine levels and paralysis.
Our studies show that betaine is able to reduce homocysteine levels and β-amyloid-induced toxicity in a C. elegans model for Alzheimer’s disease. This effect is independent of the remethylation pathway but requires the transsulfuration pathway mediated by cystathionine-β-synthase.
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Nutrient-induced Mitochondrial Activation (NiMA): A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers papers.ssrn.com
The mechanisms of mitochondrial dysfunction in Alzheimer’s Disease (AD) are incompletely understood. We show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. NiMA was also disrupted in fibroblasts derived from a patient with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity, and links mitochondrial dysfunction to AD by a mechanism dependent on soluble building blocks of plaques and tangles. https://ssrn.com/abstract=3188445
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Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1 papers.ssrn.com
Abstract
Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.
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Abstract
Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep.
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Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. - PubMed - NCBI www.ncbi.nlm.nih.gov
Adamsky, A., et al. (2018). Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell 174, 59–71.
Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased. In vivo, astrocytic activation enhanced memory allocation; i.e., it increased neuronal activity in a task-specific way only when coupled with learning, but not in home-caged mice. Furthermore, astrocytic activation using either a chemogenetic or an optogenetic tool during acquisition resulted in memory recall enhancement on the following day. Conversely, directly increasing neuronal activity resulted in dramatic memory impairment. Our findings that astrocytes induce plasticity and enhance memory may have important clinical implications for cognitive augmentation treatments.
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You probably already know that ambient light regulates circadian rhythms by interacting with light-sensitive neurons in the eye.
But let’s review anyway: In full white light (which contains all colors of light), the rays of the blue and green light spectrum activate melanopsin, a photosensitive protein in specific cells of the retina in the back of the eye. When light hits these cells, a signal transmits information to the brain’s master clock. By detecting various intensities and tones of light, the brain can keep track of what time of day it is.
This is relatively well established. We also know that sunlight can stimulate the production of vitamin D and nitric oxide, both of which have important effects on health. But are these all of the effects that light has on our physiology?
It has been known for several decades that a small percentage of blue light can penetrate human skin, and can even reach white subcutaneous adipose tissue. But the relevance of this finding on our physiology was not obvious.
Curiously, it has also been reported that high OPN4 (the gene that encodes the photopigment melanopsin) mRNA levels are found in human subcutaneous fat. Kind of weird: what the heck are these light-sensitive eye proteins doing in our fat tissue? Additionally, we now know that fat cells contain transient receptor potential cation (TRPC) channels – membranes that are found in the retina that open in response to varying intensities of light.
So, we know that blue light can get to subcutaneous fat tissue, and fat cells seem to have the machinery needed to respond to the signal that is transmitted by light. Very interesting. Is it possible that visible light penetrates the skin, and exerts physiological effects by activating a melanopsin / TRPC channel signaling pathway in human fat? And if so, could exposure to visible light have an impact on the regulation of body fat? The answer appears to be yes.
My guest in this episode (inadvertently) found the answer to this novel questions…
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People that have their deep sleep cycle disrupted for one night experience a 10% increase in amyloid plaque levels. www.sciencedaily.com
People that have their deep sleep cycle (slow-wave cycle) disrupted for one night experience a 10% increase in amyloid plaque levels compared to when their deep sleep cycle is uninterrupted.
Amyloid beta plaques accumulate outside of neurons in the brain and disrupt synapses (the connections between two neurons that form memories) and is just one way that memory loss occurs in Alzheimer’s disease.
This study showed that slow-wave sleep, which is the deep sleep that people need to wake up feeling rested, is important for preventing the accumulation of amyloid plaques. While a few nights of disrupted sleep is likely not a problem, it is the chronic disrupted slow-wave sleep (ie. sleep apnea) that may put a person at increased risk for Alzheimer’s disease.
A few things that I have found improve my sleep are switching all blue lights off before sunset since blue light stops the production of melatonin. I have red lights that turn on before sunset and this has really helped my sleep pattern. Also, a bright light exposure first thing in the morning to start my circadian clock has really helped. Lastly, following a time-restricted eating pattern where I do not eat 4 hours before bed and a cold/quiet room also make a huge difference.
My podcast with Dr. Satchin Panda discusses the importance of dark/light and food timing in sleep. Dr. Satchin Panda podcast: https://youtu.be/-R-eqJDQ2nU
My podcast with Dan Pardi also discusses ways to optimize sleep. Dan Pardi podcast: video: https://youtu.be/VhMjrWlWhLU
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Mitochondria Initiate and Regulate Sarcopenia journals.lww.com
Mitochondrial-regulated apoptosis provides a strong signaling network that contributes to sarcopenia (8). We have taken the perspective that both neural and muscle components contribute to muscle wasting, but mitochondrial health is central to initiating and perpetuating the signal for sarcopenia. We argue that mitochondrial dysfunction leads to increased mPTP opening and initiates apoptotic signaling in muscle cells and motor neurons. In aging, this is not corrected because mitophagy is inhibited. Proteasome activation leads to removal of cellular contents close to the site of dysfunctional mitochondria, and this cellular dismantling expands proportionally to the accumulation of dysfunctional mitochondria. Although aging induces widespread systemic mitochondrial dysfunction, perhaps as a result of high ROS or accumulation of mtDNA damage, we have considered that retrograde and anterograde communication likely exists between dying muscle and motor neurons, which may accelerate death in both compartments. Additional studies are needed to establish if exercise and nutrition can be used to effectively improve mitochondria health and reduce sarcopenia in aging populations. In our view, targeting dysfunctional mitochondria and increasing healthy mitochondria in motor neurons and muscle fibers provide the best strategy for reducing sarcopenia.
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Whole Coffee Fruit Concentrate – Amping Up Growth Hormone for Brain Cells - See more at: http://www.drperlmutter.com/coffee-fruit-concentrate-and-brai www.drperlmutter.com
But now there is even more excitement in terms of BDNF. A novel nutritional supplement, whole coffee fruit concentrate, has recently been shown to have a dramatic effect, in humans, in terms of raising BDNF. In a recent report in Food and Nutrition Sciences, researchers demonstrated how whole coffee fruit concentrate (WCFC) affected BDNF levels in humans. The study involved 20 young adults (25-35 years) who were asked to consume whole coffee fruit concentrate powder followed by blood evaluations of their BDNF levels. Remarkably, BDNF levels actually doubled in those individuals taking the whole coffee fruit concentrate in comparison to those who were given coffee or a placebo. - See more at: http://www.drperlmutter.com/coffee-fruit-concentrate-and-brain-cells/#sthash.g9l4Ss72.dpuf
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heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract www.neurobiologyofaging.org
(From Life Extension.com/magazine) In a 2005 article published in the journal Neurobiology of Aging, Rachel Galli and her colleagues, also based at Tufts, reported discovering a specific mechanism by which blueberries help reverse the neurological aging process.16 The Galli study—which included Drs. Joseph and Shukitt-Hale as co-investigators—sought to measure the heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract compared to a control group of aged rats. A protective mechanism produced in the brains of most animals (and humans), heat-shock proteins fight free radicals and inflammation-inducing agents, acting similarly to antioxidants to support healthy brain tissues. As people age, however, their ability to generate heat-shock proteins in sufficient quantity declines,17 sometimes dramatically. The Tufts researchers sought to determine whether blueberries could help restore the heat-shock protein response in rats.16
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Study finds women rated the most "neurotic" found to be pre-disposed to a 2-fold increased risk of Alzheimer's disease. www.cbsnews.com
A few things to know about this particular study:
- It was done in women… this doesn’t necessarily mean the effect doesn’t exist in some form in men (they just don’t know).
- Personality assessment was done using something called the Eysenck Personality Inventory, which is a commonly administered test to rate a person’s disposition, emotional stability and relative tendency toward introversion, associated with shyness or reserve, or extraversion, used to describe more outgoing people.
- Stress was defined as anything stirring feelings of anxiety, irritability, tension, fear, nervousness or sleep disturbances.
- Being extroverted or introverted on its own did not appear to heighten the risk of dementia, although the study found that women who were easily distressed and also tended to be introverted were at the highest risk for Alzheimer’s.
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The reason old folk sleep less found: neurons responsible for regulating sleep patterns in "ventrolateral preoptic nucleus" die off www.huffingtonpost.com
The method by which this area was found to be critical is particularly interesting.
FTA:
Saper analyzed a dataset of almost 1,000 subjects who had entered into a memory and aging study back in 1997, when they were all healthy 65-year-olds. As part of the study, they had all agreed to wear a small watch-sized device on their wrists for about 7 to 10 days, every two years, that would record all their movements. Upon their deaths, their brains were donated to science, so research could continue.
Saper chose 45 brains to examine, based on whether or not the ventrolateral preoptic nucleus was still intact. First he stained the brain in order to find the cluster of neurons, which were located in a similar part of the human brain as the rats' brains.
Then he linked the neurons found in the brain to the rest-activity behavior data collected in that person’s final year of life. He found that the fewer neurons one had, the more sleep fragmentation that person experienced in the last year of life. Brains with the largest amount of neurons (over 6,000) belonged to people with longer, uninterrupted sleep.
Another key finding from the study: The link between fewer neurons and less sleep was even more pronounced in people who had died with Alzheimer’s disease.