Brain Ponderings podcast with Dr. Mark Mattson

Professor Ann Mckee has spent untold hours looking at the brains of former NFL players under the microscope. She has found that nearly all of them exhibit abnormalities characterized by the presence of multiple islands of degenerating neurons surrounding small blood vessels. The affected neurons contain an abnormal (hyperphosphorylated) form of the protein Tau. The severity of the brain pathology is correlated with how long the individual played football and so the cumulative number of hits to the head they experience. CTE pathology occurs prominently in the prefrontal cortex a brain region that is important for control of emotions, working memory, and decision-making. Prior to their death these players exhibit behavioral abnormalities including outbursts of anger, confusion, poor decision-making, and depression. Dr. Mckee talks about her efforts to: understand how the disease develops, how it might be diagnosed early in the disease process, and potential ways of reducing risk for and treating this devastating brain disease. Links: Boston University CTE Center: https://www.bu.edu/cte/about/leadership/ann-mckee-md/ PBS Frontline documentary 'League of Denial': https://www.youtube.com/results?search_query=league+of+denial CTE Diagnosis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166432/pdf/NEUROLOGY2020137927.pdf CTE in NFL players: file:///Users/markmattson/Downloads/jama_mez_2017_oi_170072%20(1).pdf CTE neuropathology: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028120/pdf/nihms810306.pdf

Neuronal networks in the prefrontal cortex mediate our thoughts and control our actions and emotions. Professor Amy Arnsten of Yale University talks about the research that has established the normal functions of prefrontal cortex neuronal circuits and how dysregulation of those neuronal circuits can result in depression, schizophrenia or Alzheimer's disease. The conversation revolves around a particular type of neuron with unique properties that are critical for working memory and reflective thought. Links to videos on Yale Med School Youtube channel: https://www.youtube.com/watch?v=DEtnoiKGDwI&t=155s https://www.youtube.com/watch?v=TsQUeNuvIDY https://www.youtube.com/watch?v=wa3dWrszpEQ&t=22s Links to some of professor Ansten's reviews: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983919/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567669/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203737/ https://pubmed.ncbi.nlm.nih.gov/23040817/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907136/ Links to papers on Patricia Goldman-Rakic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767966/ https://doi.org/10.1016/S0896-6273(03)00685-8

In contrast to the dormancy of the body during sleep, neuronal networks in the brain exhibit complex patterns of activity that are important for the consolidation of memories of specific events experienced in the preceding day(s). In this podcast I talk with professor Antoine Adamantidis at the University of Bern in Switzerland whose laboratory is revealing the nature of the activities of individual neurons and neuronal networks during sleep – wake cycles. Using cutting-edge "optogenetic" technology his research has established the critical roles of neuron located in the hypothalamus and other brain regions in the control of sleep states and in the consolidation of memories. This research is leading to new approaches for improving sleep quality in ways that enhance daytime cognitive function, reduce the risk of psychiatric and age-related brain disorders, and improve recovery from a stroke or traumatic brain injury. Recent publications of Professor Adamantidis: Sleep and eating behavior: https://www-clinicalkey-com.proxy1.library.jhu.edu/service/content/pdf/watermarked/1-s2.0-S0166223621001831.pdf?locale=en_US&searchIndex= Narcolepsy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215265/pdf/zsz296.pdf Decoupling of cell body and dendrites during REM sleep: https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.abk2734 Review articles on sleep: https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-psych-010419-050815 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286245/pdf/nihms648813.pdf

Dr. Victor Navarro at Harvard Medical School talks about the control of reproduction by neurons in the hypothalamus that produce a small protein called 'kisspeptin'. It turns out that kisspeptin neurons play critical roles in the regulation of the onset of puberty, the production of eggs and sperm, ovulation, and menopause. Energy (calorie) intake can have profound effects on reproduction. For example, severe caloric restriction during early life retards the onset of puberty and inhibits estrous cycles in adult females. On the other hand childhood obesity accelerates onset of puberty, and adult obesity can cause sexual dysfunction and infertility. Dr. Navarro talks about the influence of energy balance on kisspeptin neurons and reproduction, and the potential of kisspeptin-based therapies for reproductive disorders. Links: Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852368/pdf/nihms-1778788.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159845/pdf/nihms-1569705.pdf Talk on kisspeptin and sexual behaviors: https://www.youtube.com/watch?v=e5updgoSLGE

Professor Larry Young of Emory University has elucidated some of the neurochemicals and brain circuits involved in social behaviors including pair bonding, maternal and paternal behaviors, social recognition, empathy, and grieving. Here he talks about the important roles of oxytoxin, vasopressin, and dopamine in these social behaviors. His research holds promise for developing interventions for disorders of social behavior such as autism and social anxiety disorders. Links: The Chemistry Between Us: Love, Sex, and the Science of Attraction: https://www.amazon.com/Chemistry-Between-Us-Science-Attraction/dp/1591846617 Lecture: https://www.youtube.com/watch?v=BXUd0gblPfM&t=4155s Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604207/pdf/nihms-1752167.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283620/

The seeming ease with which we perform everyday tasks with our hands belies the complexity of the nerve cell circuits that control them. Professor Sliman Bensmaia is a professor at the University of Chicago where his laboratory works to understand how the brain controls hand movements. He is using this knowledge to develop bionic hands that sense touch and control the movements of the fingers and wrist. Here he talks about his research and its applications for people who have suffered an arm amputation or are paralyzed by a spinal cord injury. LINKS Professor Bensmaia's webpage: https://bensmaialab.github.io/ Review article on manual dexterity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169115/pdf/nihms-1796186.pdf Review article on the science and engineering of bionic hands: https://journals-physiology-org.proxy1.library.jhu.edu/doi/epdf/10.1152/physrev.00034.2020 Professor Besnmaia lectures: https://www.youtube.com/watch?v=x-2hB32BZTw https://www.youtube.com/watch?v=tQt8AgES7wc&t=25s

Kevin Tracey is a professor of bioelectronic medicine and president of the Feinstein Institutes for Medical Research in New York. His research discoveries identified a previously unknown neural pathway by which the brain senses and responds to inflammation in peripheral organs. During inflammation macrophages release a cytokine called TNF which triggers a neural reflex mediated by the vagus nerve. This "inflammatory reflex" response suppresses the tissue inflammation. This discovery led to the testing of vagus nerve stimulation in several disorders including rheumatoid arthritis, Crohn's disease, and stroke. Tracey describes his trail of discoveries and talks about the promising future of bioelectronic medicine. Dr. Tracey's webpage: https://feinstein.northwell.edu/institutes-researchers/our-researchers/kevin-j-tracey-md TEDMED talk: https://www.youtube.com/watch?v=AJH9KsMKi5M Review articles http://perspectivesinmedicine.cshlp.org/content/10/3/a034140.long file:///Users/markmattson/Downloads/nn.4477%20(1).pdf

Chronic pain is common and places major burdens on affected individuals, their families, and health care systems. Available treatments are often ineffective and in the case of opioids are highly addictive. Here professor Stephen Waxman of Yale University School of Medicine talks about the discovery of genes that encode proteins in the sensory neurons that convey pain signals. Studies of families in which pain syndromes are inherited identified three such "pain genes" each of which encodes a sodium (Na+) channel in neurons that sense pain. Waxman has shown that mutations in one of the Na+ channels – Nav1.7 – result in hyperexcitability of the neurons and chronic extreme pain. He is working with pharmaceutical companies to develop drugs that selectively block Nav1.7 and so reduce pain. This research is likely to lead to non-addictive drugs that are effective in reducing or eliminating pain. Links: Professor Waxman's webpage: https://medicine.yale.edu/profile/stephen_waxman/?tab=news Book "Chasing Men on Fire: The Story of the Search for the Pain Gene: https://www.amazon.com/Chasing-Men-Fire-Story-Search/dp/0262037408 Sodium channels and pain: https://journals.physiology.org/doi/epdf/10.1152/physrev.00052.2017 Pain Resilience: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519173/pdf/nihms-1585946.pdf

Everyone enjoys music and some are skilled in producing music. Neuroscientist and opera singer Indre Viskontas has worked to understand how the brain processes and generates music, and how music can be used to help people with neurological disorders such as Parkinson's and Alzheimer's disease. Here she talks about her experiences growing up in a musical family and becoming a neuroscientist, and her research at UCLA and the University of San Franscisco and the San Francisco Conservatory of music. Dr. Viskontas is the hose of the "Inquiring Minds" podcast and the author of the book "How Music Can Make You Better" Indre's webpage: https://www.indreviskontas.com/ Inquiring Minds podcast: https://inquiring.show/ San Francisco Conservatory of Music: https://sfcm.edu/ University of San Francisco webpage: https://www.usfca.edu/faculty/indre-viskontas Review article: "Music in the Brain": file:///Users/markmattson/Downloads/s41583-022-00578-5%20(1).pdf

Developmental neurobiologist Mahendra Rao has been at the forefront of human stem cell research for three decades. In this episode he describes advances in research on human embryonic stem cells and patient-derived stem cells that is aimed at replacing the neurons that die in diseases such as Parkinson's, Alzheimer's and ALS. Dr. Rao is the former director of the NIH Center for Regenerative Medicine and is currently the CEO of Pancella. Lecture by Dr. Rao https://www.youtube.com/results?search_query=mahendra+rao+stem+cells Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919381/pdf/12015_2016_Article_9662.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912385/pdf/main.pdf NIH Center for Regenerative Medicine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883278/pdf/scd.2013.0437.pdf