Neurotransmitter
Episodes
In this clip, Wim Hof describes how he controls his breath to deal with the discomfort of the cold.
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In this clip, Wim Hof describes how he controls his breath to deal with the discomfort of the cold.
Topic Pages
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Depression
Depression involves dysregulated monoaminergic neurotransmission—serotonin, norepinephrine, dopamine—impairing synaptic plasticity and fronto-limbic mood circuits.
News & Publications
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Lifelong choline supplementation provides a potential shield against Alzheimer's disease in mice. www.ncbi.nlm.nih.gov
Choline, an essential nutrient found in eggs, meat, fish, beans, and nuts, supports the production of acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. Most people living in the US don’t consume enough choline – 550 milligrams per day for men and 425 milligrams per day for women – potentially increasing their risk for various diseases. A 2019 study in mice found that lifelong choline supplementation prevented Alzheimer’s disease and preserved cognitive function.
Researchers fed mice susceptible to developing Alzheimer’s disease a regular diet or a diet supplemented with choline from early life to old age. When the mice reached the age of 10 months, the researchers assessed the animals' memory function and examined their brain tissue.
They found that mice that received lifelong choline supplementation had better spatial memory and fewer amyloid-beta plaques in their brains than those on a regular diet. They also found that the mechanisms driving these effects were related to reduced amyloid-beta peptide synthesis, a dampened microglia inflammatory response, and downregulation of the alpha-7 nicotinic acetylcholine and sigma-1 receptors, both of which are critical for various neurological processes.
These findings suggest that lifelong choline supplementation mitigates Alzheimer’s disease pathology and maintains cognitive function in mice susceptible to the disease. Other research showed that mice that ate a choline-poor diet had higher brain levels of amyloid-beta and tau – two proteins implicated in the pathogenesis of Alzheimer’s disease – than those that ate a choline-rich diet. The mice that ate a choline-poor diet also gained weight, showed signs of altered metabolism, liver damage, and enlarged hearts, and performed poorly on motor skills tests.
More than 55 million people worldwide live with Alzheimer’s disease. Learn more about the disease and how to prevent it in this episode featuring Dr. Dale Bredesen.
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Pregnancy hormones drive neurological changes in mice, inducing maternal behavior. www.sciencedaily.com
Pregnancy induces marked changes in the female body to prepare for birth, lactation, and the responsibilities of motherhood. A growing body of evidence suggests pregnancy also changes the female brain. A recent study in mice shows that estrogen and progesterone alter galanin-producing neurons in the brain, switching on maternal behavior before offspring arrive.
Researchers analyzed the effects of various pregnancy-related hormones on the brain activity of pregnant mice. Then they blocked the activity of the hormones and assessed the animals' behavior.
They found that estrogen dampened the baseline activity of galanin-expressing neurons in the hypothalamus while increasing their responsiveness. Progesterone reshaped the neurons' connections by driving more synapse formation. Blocking the two hormones' influence in pregnant mice prevented the emergence of maternal behavior, even after giving birth.
Galanin is a neurohormone and neurotransmitter produced in the central nervous system, particularly the hypothalamus. It plays versatile physiological roles in the neuroendocrine axis, such as regulating food intake and insulin levels and driving maternal and fetal weight gain during pregnancy.
These findings suggest that female hormones alter the brain during pregnancy, inducing maternal behaviors and ultimately influencing offspring survival. Learn how maternal health influences offspring health in this clip featuring Dr. Elisa Eppel.
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Ketogenic diet may alleviate ADHD symptoms by altering gut microbiota and boosting neurotransmitter expression. journals.plos.org
Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral condition observed in children and adults. A recent study in mice suggests that a ketogenic diet reduces symptoms of ADHD via alterations in the gut microbiota.
Researchers conducted experiments using two groups of rats: one with ADHD-like symptoms and another without. They further divided each group into three subgroups: those fed a standard diet, those treated with methylphenidate (an ADHD drug commonly sold as Ritalin, Concerta, or others), and those fed a ketogenic diet.
They found that both the methylphenidate and ketogenic diet interventions reduced ADHD-like behaviors, such as increased activity and hypermobility. In addition, both groups demonstrated elevated levels of various neurotransmitters, including serotonin, norepinephrine and others, in brain tissue, along with changes in the expression of key proteins related to neural signaling. Interestingly, the ketogenic diet also altered the gut microbial composition in ADHD-like rats, especially microbes involved in amino acid and sugar metabolism.
These findings suggest that the ketogenic diet may hold promise as a novel approach for mitigating ADHD-related behavioral challenges, possibly by influencing the gut microbiota. It also underscores the robust effects the ketogenic diet has on the brain. Learn more in this clip featuring Dr. Dominic D'Agostino.
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Maternal vitamin D deficiency linked to potential developmental disorders, emphasizing a role in dopamine signaling. neurosciencenews.com
Dopamine is a neurotransmitter best known for its role in motor, motivation, and pleasure control. A new study highlights vitamin D’s influence on dopamine signaling and emphasizes its essential role in the normal development of dopamine-producing cells.
Researchers developed three cell lines to mimic the natural process of embryonic development, during which cells differentiate (specialize) into dopamine-producing neurons. Then they cultured the cells in the presence or absence of vitamin D.
They found that vitamin D participated in neuronal growth and branching, the rearrangement of presynaptic proteins, and the production and release of dopamine. The researchers posited that glial-derived growth factor, a vitamin D-dependent factor that promotes dopamine neuron differentiation, was the mechanism driving these effects.
These findings suggest that vitamin D plays multiple roles in dopamine signaling, with potential implications for neurodevelopmental disorders like schizophrenia, ADHD, and autism. They also underscore the importance of adequate maternal vitamin D status during pregnancy.
Interestingly, vitamin D and omega-3 fatty acids may synergistically work to support neurodevelopment further. Read this open-access peer-reviewed article by Dr. Rhonda Patrick to learn more.
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Memory-enhancing effects of hippocampal estrogen receptor activation involve metabotropic glutamate receptor signaling, mouse study suggests. (2013) www.sciencedaily.com
From the article:
The research, published in the the Journal of Neuroscience today, focused on estrogen effects in a brain region called the hippocampus, which deteriorates with age or Alzheimer’s disease. The researchers found that each of the two known estrogen receptors rapidly activate a specific cellular pathway necessary for memory formation in the hippocampus of female mice, but only if they interact with a certain glutamate receptor, called mGluR1.
The study revealed that when this glutamate receptor is blocked, the cell-signaling protein ERK cannot be activated by the potent estrogen, 17β-estradiol. Because ERK activation is necessary for memory formation, estradiol failed to enhance memory among mice in which mGluR1 was blocked.
Frick’s team also found evidence that estrogen receptors and mGluR1 physically interact at the cell membrane, allowing estradiol to influence memory formation within seconds to minutes.
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Neuron-derived estrogen may regulate synaptic plasticity and memory, mouse study suggests. (2019) www.sciencedaily.com
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.
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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.
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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.
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The brain may be capable of rapidly producing and releasing large amounts of estrogen, animal study suggests. (2013) www.sciencedaily.com
From the article:
“Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us,” says Ei Terasawa, professor of pediatrics at the UW School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. “These findings not only shift the concept of how reproductive function and behavior is regulated but have real implications for understanding and treating a number of diseases and disorders.”
For diseases that may be linked to estrogen imbalances, such as Alzheimer’s disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. “Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases.”
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In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges.
In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain.
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Leading up to this discovery, Terasawa said, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats.
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High-dose testosterone treatment increased serotonin transporter binding in transgender people. (2015) www.sciencedaily.com
From the article:
As they grow older and as their sex hormone output falls, men suffer more commonly from depression and some studies have already demonstrated a positive effect of testosterone supplementation on the moods of the test subjects. Now, the study led by Rupert Lanzenberger from the University Department of Psychiatry and Psychotherapy has demonstrated for the first time worldwide that testosterone increases the number of serotonin transporters (proteins) in the human brain. These proteins regulate the concentration of serotonin and are also the target for antidepressants.
Serotonin transporters increased after just four weeks of hormone therapy
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“The study has shown that testosterone increases the potential binding sites for commonly prescribed antidepressants such as SSRIs in the brain and therefore provides major insights into how sex hormones affect the human brain and gender differences in psychiatric illnesses,” says Siegfried Kasper, Head of the University Department of Psychiatry and Psychotherapy at the MedUni Vienna.
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higher acid-sphingomyelinase associated with disease progression in Alzheimer's www.ncbi.nlm.nih.gov
“Pharmacological restoration of ASM to the normal range improves pathology in AD mice The ASM-mediated lysosomal/autophagic dysfunction in AD prompted us to examine possible therapeutic implications of this pathway. To decrease ASM in APP/PS1 mice, we undertook pharmacological inhibition using amitriptyline-hydrochloride (AMI) for 4 mo (Fig. 9 A). AMI is a known inhibitor of ASM that can cross the blood–brain barrier. At 9 mo of age, AMI-treated APP/PS1 mice exhibited decreased ASM activity compared with vehicle-treated mice (Fig. 9 B). Other sphingolipid metabolites were not changed (Fig. 9 C). Aβ levels were decreased in the AMI-treated APP/PS1 mice compared with the nontreated littermates.”
“ASM activity is known to be increased by environmental stress and in various diseases, and is elevated in AD patients (He and Schuchman, 2012). One downstream consequence of increased ASM is elevated ceramide, contributing to cell death, inflammation, and other common disease findings. Although elevated ASM is known to occur in AD, the cellular mechanisms that link ASM and AD have not been fully characterized. The data presented here suggest a previously unknown role of ASM in the down-regulation of lysosomal biogenesis and inhibition of lysosome-dependent autophagic proteolysis. The findings also establish proof of concept for ASM inhibitor therapy in AD.”
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Food Additives Causing Harm, Reforms Urgently Needed, AAP Says www.medscape.com
The Worst Offenders:
The statement addresses 2 broad categories of additives: direct and indirect. Indirect additives refers to substances in “food contact materials,” such as “adhesives, dyes, coatings, paper, paperboard, plastic, and other polymers,” the authors of the policy statement explain. Direct food additives include chemicals such as colorings, flavorings, and preservatives added to food during processing. Within those two categories the authors identified six types of additives of most concern, based on accumulating evidence summarized in the report and in an accompanying press release:
Bisphenols: Used to manufacture plastic containers and food and beverage cans, these compounds have been associated with endocrine and neurodevelopmental disruption and obesogenic activity, with alterations in the timing of puberty, reduced fertility, and impaired neurological and immunological development. One bisphenol, bisphenol A, has already been banned from baby bottles and sippy cups. Phthalates: As components of plastic wrap and plastic tubing and containers, phthalates similarly have been implicated in endocrine disruption and obesogenic activity. "A robust literature" shows that these chemicals adversely affect male sexual development, may contribute to childhood obesity and insulin resistance, and may also contribute to cardiovascular disease. Perfluoroalkyl chemicals: These chemicals are used in the manufacture of greaseproof paper and cardboard packaging. They have been associated with immunosuppression, endocrine disruption such as impaired thyroid function, and decreased birth weight. Perchlorate: Often added to plastic packaging for dry foods to control static electricity, perchlorate has been shown to disrupt production of thyroid hormone, with implications for subsequent cognitive function. Of particular concern is exposure among pregnant women, "given that the developing fetus is entirely reliant on the maternal thyroid hormone during the first trimester of pregnancy," the authors write in the technical report. They suggest that perchlorate "may be contributing to the increase in neonatal hypothyroidism and other thyroid system perturbations that have been documented in the United States." Nitrates and nitrites: As direct food additives, these compounds are used as preservatives and color enhancers in cured and processed meats, fish, and cheese. There has been "longstanding concern" over their use, the authors write, because of an association with cancers of the nervous and gastrointestinal systems, and methemoglobinemia in infants. They were classified as "probable human carcinogens" in 2006 by the International Agency for Research on Cancer. Artificial food colors: Often added to products that appeal to children, such as juice drinks, artificial food colors have been associated in some studies with an increased risk for attention-deficit hyperactivity disorder. Although their mechanisms of action are not yet completely understood, and the research "should be interpreted with caution," the authors recommend "a thorough reassessment" of artificial food colors to ensure they are safe. -
Known alcohol-dependence gene Nf1 gene linked to GABA neurotransmitter. Mice with this functional gene steadily increase alcohol after withdrawal. www.sciencedaily.com
FTA:
The team tested several behavioral models, including a model in which mice escalate alcohol drinking after repeated withdrawal periods, to study the effects of partially deleting Nf1. In this experiment, which simulated the transition to excessive drinking that is associated with alcohol dependence in humans, they found that mice with functional Nf1 genes steadily increased their ethanol intake starting after just one episode of withdrawal. Conversely, mice with a partially deleted Nf1 gene showed no increase in alcohol consumption.
Looks like the authors of this paper may be looking at epigenetic roles next?
The team sees the new findings as “pieces to the puzzle.” Sanna believes future research should focus on exactly how Nf1 regulates the GABA system and how gene expression may be altered during early development.