Brain Ponderings podcast with Dr. Mark Mattson

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

Professor Mike Merzenich of the University of California San Francisco has spent over six decades working to elucidate how sensory inputs – particularly sounds, sights, and touch – affect the structure and function of neuronal networks. In this episode he recounts his major discoveries and contributions to the understanding of neuroplasticity and to the development of tools for restoring and enhancing neuroplasticity including the invention of the cochlear implant and the brain training software 'Brain HQ'. The book 'Soft-Wired' by Michael Merzenich: https://www.amazon.com/Soft-Wired-Science-Brain-Plasticity-Change/dp/0989432823 Review articles by Merzenich: Development of the cochlear implant: https://reader.elsevier.com/reader/sd/pii/S037859551400207X?token=498168B45106A73637B08A11326B439B9DDCC769094D0CFA2A42CFAB19A3E1175A415223059084038220ABBB4266E8FA&originRegion=us-east-1&originCreation=20220909122717 Neuroplasticity-based therapeutics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072971/pdf/fnhum-08-00385.pdf 'BrainHQ' website: https://v4.brainhq.com/?v4=true&fr=y#survey/ftux

Stroke and dementia are major causes of long-term disability. Unfortunately, there are currently no treatments that are effective in restoring brain function in these disorders. In this episode neurologist and neuroscientist Tom Carmichael at UCLA describes research that aims to restore brain function using regenerative medicine approaches that stimulate the formation of new neuronal connections or replace neurons that have died. Links: https://www-nature-com.proxy1.library.jhu.edu/articles/s41583-020-00396-7.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916498/pdf/nihms950783.pdf

Adaptations that enhanced the abilities to acquire, store, and efficiently utilize the energy in foods were of fundamental importance in brain evolution. In this episode professor Alan Watts of the University of Southern California describes the complicated elegant ways in which the brain regulates food intake including neuroendocrine systems, feedback signaling from the body to the brain, and neuronal networks involved in reward, learning and memory, and decision-making. Advances in understanding the neural systems that control appetite and energy balance are providing avenues for interventions to combat the epidemic of obesity. Links: Review article on the control of eating by professor Watts and colleagues: file:///Users/markmattson/Downloads/physrev.00028.2020%20(1).pdf

What was; what is; what if, what might be? Imagination pervades our daily lives as we think about the past and envision the future. Importantly, we use our imagination to create new and meaningful things – works of art to books, buildings, automobiles, computers, scientific discoveries, etc. Creativity can be fostered in children and enhanced throughout life. Here I talk with Anna Abraham whose research is elucidating the neurobiology of imagination and creativity. She is currently a professor of educational psychology, and director of the Torrance Center for Creativity and Talent Development at the University of Georgia. Links Book: The Neuroscience of Creativity: https://www.amazon.com/Neuroscience-Creativity-Cambridge-Fundamentals-Psychology/dp/1316629619 Review article: The Imaginative Mind: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867574/pdf/HBM-37-4197.pdf Torrance Center webpage: https://coe.uga.edu/directory/torrance-center

Rehana Leak who is an Associate Professor of Pharmacology at Duquesne University and I discuss how cells respond adaptively to various types of mild stress by processes that fall under the umbrella of "hormesis". During evolution organisms acquired many different ways of coping with and even using to their advantage of potentially damaging environmental factors such as exposures to metals, toxic gases, extreme temperatures, food scarcity, etc. Research findings show that various means of engaging adaptive stress response signaling pathways can be deployed to enhance brain performance and protect neurons against various neurological disorders. Book: Hormesis: A Revolution in Biology, Toxicology, and Medicine: https://www.amazon.com/Hormesis-Revolution-Biology-Toxicology-Medicine/dp/1627038515 Lecture on hormesis: https://www.youtube.com/watch?v=ZpcVku45hFY Review articles on hormesis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096685/pdf/10.1177_1559325818784501.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248601/pdf/nihms39393.pdf Scientific American article: 'What doesn't kill you…': https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841445/pdf/nihms946635.pdf

Posttraumatic stress disorder (PTSD) is a debilitating condition triggered by experiencing or witnessing a terrifying event. The symptoms of PTSD include severe anxiety, flashbacks, nightmares, and panic. Kerry Ressler who is a Professor of Psychiatry at Harvard Medical School describes recent findings of neuroscientists and clinicians that have advanced an understanding what goes wrong in the brain in PTSD and how people with PTSD are benefiting from emerging therapies. Links: Lectures on PTSD by Dr. Ressler: https://www.youtube.com/watch?v=TRHBMI7r-xM&t=2057s https://www.youtube.com/watch?v=51zkpRuvpQY https://www.youtube.com/watch?v=51zkpRuvpQY Review article on PTSD: https://www-nature-com.proxy1.library.jhu.edu/articles/s41582-022-00635-8.pdf

There are as many astrocytes in the human brain as there are neurons, but the functions of astrocytes in brain function, health, and disease are unclear. Professor Maiken Nedergaard of the University of Rochester and the University of Copenhagen describes recent discoveries that are revealing roles of astrocytes in processes such as learning and memory and how abnormalities in astrocytes may contribute to diseases such as Alzheimer's disease and mental disorders. About 10 years ago Nedergaard discovered that astrocytes control the movement of fluids throughout the brain in a system she has dubbed the brain's "glymphatic system". An important function of the glymphatic system is to remove potentially toxic molecules from the brain such as those that accumulate in the brain in Alzheimer's and Parkinson's diseases. Sleep and exercise enhance the glymphatic system which likely contributes to the beneficial effects of sleep and exercise on brain health. Links: Professor Nedergaard's Lab page: https://www.urmc.rochester.edu/labs/nedergaard.aspx Review on the brain's glymphatic system: https://journals-physiology-org.proxy1.library.jhu.edu/doi/epdf/10.1152/physrev.00031.2020 Glymphatic system and Alzheimer's disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186542/pdf/nihms-1707936.pdf