News & Publications

• Gut microbes from Alzheimer's patients impair memory and neurogenesis in rats, suggesting a link between gut health and Alzheimer's disease. www.kcl.ac.uk
  Brain Alzheimer's Gut Microbiome Memory Neurogenesis

  The hippocampus, a small organ within the brain’s medial temporal lobe, is critical for memory, learning, and spatial navigation. The loss of hippocampal neurogenesis (the formation of new neurons) is an early indicator of Alzheimer’s disease. A recent study in rats shows that gut microbial transplants from people with Alzheimer’s inhibit hippocampal neurogenesis and impair memory.

  Researchers transplanted gut microbes from healthy older adults or those with Alzheimer’s disease into the guts of young adult rats. Then, using behavioral tests, they assessed the rats' cognitive function.

  They found that the rats that received transplants from people with Alzheimer’s exhibited impaired memory and altered mood – functions that rely on hippocampal neurogenesis. The extent of these impairments correlated with the donors' cognitive abilities and the presence of inflammation-promoting microbes. They also noticed differences in microbial metabolites in the rats' guts, including taurine, an amino acid that supports hippocampal neurogenesis.

  These findings suggest that symptoms of Alzheimer’s disease can be passed on to a healthy, young individual via the gut microbiota, confirming the role of the gut microbiota in causing Alzheimer’s. They also highlight the importance of developing and maintaining a healthy gut microbial population, a process that begins early in life. Learn more in this clip featuring Dr. Eran Elinav.

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• Extreme microdose of THC from cannabis (three to fou orders of magnitude lower than standard dose) produces long-term neuroprotection in mice subjected to acute neurological insults. www.frontiersin.org
  Brain Aging Cannabinoid Neurogenesis

  Delta-9-tetrahydrocannabinol – better known as THC – is the primary psychoactive compound found in cannabis. THC binds to endocannabinoid system receptors, eliciting a wide range of physical effects and producing the “high” associated with its use. A new study suggests that THC reverses brain aging in old mice.

  Researchers injected old mice with a microdose of THC that was roughly three to four orders of magnitude lower than a typical dose. Then, they assessed gene expression in the animals' hippocampal tissue at five days and five weeks post-treatment.

  After just five days, they found that the microdose THC treatment altered the expression of 18 genes related to neurogenesis (the production of new nerve cells). THC altered the expression of 88 genes related to nerve cell survival and development five weeks post-treatment. Interestingly, THC did not affect brain-derived neurotrophic factor, a protein noted for its effects on neurogenesis.

  These findings suggest that a single microdose of THC exerts potent, enduring effects on the rodent brain and may have potential applications in humans. It also aligns with results from a compelling case study in which THC microdosing ameliorated symptoms of Alzheimer’s disease. Lactate, a molecule produced during vigorous exercise, also has robust effects on the brain, influencing neurogenesis and promoting cognitive function. Learn more in this episode featuring Dr. George Brooks.

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• Testosterone may mediate antidepressant effects via ERK2 signaling, rat study suggests. (2012) www.sciencedaily.com
  Hormones Depression Mental Health Testosterone Neurogenesis

  From the article:

  Compared to men, women are twice as likely to suffer from an affective disorder like depression. Men with hypogonadism, a condition where the body produces no or low testosterone, also suffer increased levels of depression and anxiety. Testosterone replacement therapy has been shown to effectively improve mood.

  Although it may seem that much is already known, it is of vital importance to fully characterize how and where these effects are occurring so that scientists can better target the development of future antidepressant therapies.

  To advance this goal, the scientists performed multiple experiments in neutered adult male rats. The rats developed depressive-like behaviors that were reversed with testosterone replacement.

  They also “identified a molecular pathway called MAPK/ERK2 (mitogen activated protein kinase/ extracellular regulated kinase 2) in the hippocampus that plays a major role in mediating the protective effects of testosterone,” said Kabbaj.

  This suggests that the proper functioning of ERK2 is necessary before the antidepressant effects of testosterone can occur. It also suggests that this pathway may be a promising target for antidepressant therapies.

  Kabbaj added, “Interestingly, the beneficial effects of testosterone were not associated with changes in neurogenesis (generation of new neurons) in the hippocampus as it is the case with other classical antidepressants like imipramine (Tofranil) and fluoxetine (Prozac).”

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• Oleic acid produced by cells in the brain (and found in olive oil) may be a key cell proliferation and neurogenesis signal www.sciencedaily.com
  Brain Neurogenesis

  Oleic acid produced in the brain promotes neurogenesis – the generation of new neurons.

  Oleic acid is a monounsaturated fatty acid produced in plants and is the primary fatty acid found in olive oil. Interestingly, oleic acid is also produced in the human brain. Findings from a recent study suggest that brain-derived oleic acid activates neural stem cells in the hippocampus, promoting neurogenesis – the generation of new neurons.

  The hippocampus is a small organ located within the brain’s medial temporal lobe. It is an important part of the limbic system (the region that regulates emotions) and plays critical roles in memory, learning, and spatial navigation. The neurons in the hippocampus are particularly vulnerable to amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy – early indicators of Alzheimer’s disease.

  The investigators used spectroscopy, a research tool that uses light scatter to measure concentration, to look for the presence of monounsaturated fatty acids in neural progenitor cells. These cells differ from stem cells in that they can undergo only a limited number of replication cycles. They found that the progenitor cells contained several monounsaturated fatty acids, the most abundant of which was oleic acid. Treating the cells with a chemical that blocked the activity of enzymes involved in oleic acid production dramatically reduced the cells' survival.

  Next, they used spectroscopy to look for the presence of monounsaturated fatty acids in the brains of mice. They found an abundance of the fatty acids, especially oleic acid, in the dentate gyrus, the region of the hippocampus where neurogenesis occurs. Then, using homology modeling (a type of computer-based study technique) they observed that oleic acid bound to TLX, a protein in neural stem cells that regulates neurogenesis, switching on the protein’s activity and driving the production of new neurons.

  These findings suggest that oleic acid produced in the brain activates neurogenesis. Therapeutic modulation of TLX may be a means to counteract the effects of impaired neurogenesis in age-related cognitive decline, depression, Alzheimer’s disease, and other conditions. Brain-derived neurotropic factor, or BDNF, also promotes neurogenesis. Learn more about BDNF and the lifestyle behaviors that promote its production in our overview article.

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• Gut bacteria may alter the aging process of the human brain through the production of butyrate www.sciencedaily.com
  Brain Gut Aging Microbiome Neuron Fatty Liver Neurons Neurogenesis Butyrate

  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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