Brain Ponderings podcast with Mark Mattson

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

Christof Koch is a computational neuroscientist who is currently the chief scientist at the Allen Institute for Brain Science in Seattle. Here he talks about the cellular complexity of the brain and how neuroscientists are working to understand how brain’s process information and the biological basis of consciousness.   Links: Allen Institute for Brain Science: https://alleninstitute.org/

Ron Petersen is a neurologist at the Mayo Clinic where he has devoted his career to research aimed at understanding what happens to the brain in Alzheimer’s disease and to the development of new approaches for early diagnosis and treatment of this common neurodegenerative disorder of aging. He discusses the genetics of Alzheimer’s disease and how diet and lifestyle choices during midlife may influence one’s likelihood of developing this disorder later in life.   Links:     https://www.mayo.edu/research/faculty/petersen-ronald-c-m-d-ph-d/bio-00078363   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574196/   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005347/

Professor Judy Illes of the University of British Columbia talks about ethical considerations that have arisen from rapid advances in neurotechnologies such as genetic engineering, brain implants, and brain-computer interfaces. Everyone has a stake in neuroethics – scientists, policy-makers, the media, information technology companies, and individual citizens. Professor Illes has been working to identify major issues in neuroethics and to facilitate interactions amongst the different stakeholders.   Links: Neuroethics Canada: http://www.neuroethicscanada.ca

Dr. Bindu Paul of Johns Hopkins University discusses remarkable discoveries which showed that three ‘toxic’ gases – nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) – are produced in brain cells. Their production occurs in response to activity in neuronal networks and evidence suggests that each of these gases plays important roles in learning and memory, and the regulation of blood flow in the brain.  Diet and lifestyle factors, and drugs can affect the production of the ‘gasotransmitters’ in ways that improve brain health. Abnormalities in the regulation of these gases is believed to occur in Alzheimer’s and Huntington’s diseases, and chronic fatigue syndrome.

Professor Satchin Panda of the Salk Institute talks about his trail of discoveries concerning circadian rhythms in plants and animals that led to experiments that advanced an understanding of the importance of the timing of food consumption in human health and disease.

In this episode I converse with Professor Ted Dawson of Johns Hopkins University School of Medicine about how advances in genetics, cell biology, and clinical studies have shed light on the causes of neuron dysfunction and degeneration in Parkinson’s disease. We discuss how this information is leading to the development of new approaches for the prevention and treatment of this devastating neurodegenerative disease.

Professor Karl Friston of University College London has made major technical advances and discoveries that are revealing how the brain processes information in ways that result in appropriate behaviors.  He talks about two brain imaging methods – positron emission tomography and functional magnetic resonance imaging – and how they have advanced an understanding of how neuronal networks are organized in a functionally integrated manner. He has used brain imaging to elucidate what goes wrong in schizophrenia. More recently he developed a theory called active inference or ‘the free energy principle’ which provides a mathematical framework for how the brain processes information. This theory promises to be a valuable tool in the fields of neuroscience and artificial intelligence.