News & Publications

• 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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• 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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