Brain Ponderings podcast with Dr. Mark Mattson

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.

Why are some people susceptible to becoming addicted to a drug or developing severe depression, while others are not? Professor Eric Nestler of Mount Sinai School of Medicine talks about research suggesting one explanation: epigenetic alterations – enduring changes in the activation of certain genes – in neurons results in long-lasting changes in structure and function of neuronal networks. In addiction, repeated drug exposure results in excessive release of dopamine onto 'medium spiny neurons' in a brain region called the nucleus accumbens. Over time this leads to molecular changes in proteins called histones in the nucleus. The histones are part of molecular structures called chromatin upon which DNA is wound. By changing the structure of the chromatin the expression of genes on the associated DNA is altered in ways that contribute to addiction. Dr. Nestler's laboratory is also elucidating the roles epigenetic molecular alterations that occur as a result of chronic stress contribute to depression.

I talk with Professor Stephen Cunnane of Sherbrooke University about emerging evidence that ketones can protect neurons in the brain against dysfunction and degeneration during aging. The ability of neurons to utilize glucose as an energy source is impaired in Alzheimer's disease, but the neurons can still utilize ketones. In addition, ketones can activate genes that encode proteins that help the neuron withstand stress and form new synaptic connections.

Glioblastoma is a highly malignant and almost always fatal brain cancer. Neuro-oncologist Justin Lathia of the Cleveland Clinic shares his knowledge and research discoveries on what makes glioblastomas so nasty. The cancer cells within the tumor vary greatly in their genetic abnormalities and sensitivities to chemotherapy and radiation Particularly resistant to treatment are glioblastoma stem cells. These cancer cells interact with other cells in the brain in ways that enable them to flourish and to evade the immune system. Knowledge of these mechanisms is providing new avenues for developing effective treatments.