In this third podcast in the Bioenergetics and Brain Health series I talk about how intermittent exercise and fasting affect brain function, neuroplasticity, and resilience. Research has shown that both of these bioenergetic challenges can enhance learning and memory, improve mood, counteract aging, and protect neurons against injury and disease. I provide an overview of evidence that over periods of weeks and months cycling between challenge (exercise and fasting) and recovery (resting, eating, sleeping) periods stimulates the formation of new synaptic connections between neurons, increases neurogenesis, and bolsters neuronal stress resistance. These adaptations of brain cells to bioenergetic challenges are mediated by hormonal factors released from peripheral organs including ketones, and by changes in gene expression in brain cells. A better understanding of how bioenergetic challenges affect the brain provides a rationale for incorporating exercise and fasting into lifestyles and is also revealing new approaches for pharmacological interventions in neurological disorders.

This is the second in a series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. In this episode I describe how mitochondria are moved about within axons and dendrites, how mitochondria divide, fuse with each other, and are eliminated when they become dysfunctional. Importantly, mitochondria influence and respond to activity in neuronal networks in ways that optimize energy efficiency and promote the formation and maintenance of synapses between neurons. I also introduce the next presentation which will focus on how physical exercise and intermittent fasting affect brain function, plasticity, and resilience.

More than 40 percent of the human genome consists of retrotransposons which are DNA sequences related to retroviruses that can jump within the genome and have the ability to replicate although most are dormant. In this episode Professor Josh Dubnau at the University of Stony Brook talks about endogenous retroviruses and retrotransposons and recent evidence that some of them are activated in neurons during brain aging and may play roles in the pathogenesis of ALS, frontotemporal dementia, and Alzheimer’s disease. Using the powerful molecular genetic tools in Drosophila models the Dubnau and his team have shown that activated retrotransposons can cause pathological aggregation of the protein TDP43 in neurons and the spreading of the TDP43 pathology between cells similar to that which occurs in ALS and frontotemporal dementia. This basic research advances an understanding of brain aging and neurodegenerative disorders and suggests new approaches for preventing and treating these disorders.

LINKS

Dr. Dubnau’s web page

https://renaissance.stonybrookmedicine.edu/anesthesiology/research/Dubnau

Review article on endogenous retroviruses and retrotransposons and their putative roles in neurodegenerative disorders

https://pubmed.ncbi.nlm.nih.gov/38663088/

Original research articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC9944888/pdf/41467_2023_Article_36649.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC8096092/pdf/pgen.1009535.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC6783360/pdf/nihms-1536529.pdf