In this final episode of the Bioenergetics and Brain Health series I talk about changes that occur in brain cells during normal aging, and in Alzheimer’s disease, Parkinson’s disease, and stroke with emphasis on alterations upstream and downstream of cellular energy metabolism. The episode concludes with examples of therapeutic interventions that target those age- and disease-related alterations.

LINKS:

Hallmarks of Brain Aging

https://pmc.ncbi.nlm.nih.gov/articles/PMC6039826/pdf/nihms979409.pdf

Brain Energy Rescue:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7948516/pdf/nihms-1624328.pdf

The Hormesis Principle of Brain Health and Resilience

https://pmc.ncbi.nlm.nih.gov/articles/PMC5209274/pdf/nihms834422.pdf

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

This is the fist in a short series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. Overindulgent sedentary lifestyles are increasingly common with adverse consequences for trajectories of brain health in current and future generations. In this series I review findings from studies of humans and animals that are elucidating the cellular and molecular mechanisms by which energy intake and exercise affect structural and functional neuroplasticity. This topic is considered from a bioenergetic perspective with emphases on brain evolution, developmental neurobiology, adult neuroplasticity and disorders of mood and cognition.

Every day we communicate with and influence others via language, decision-making, and actions. The complexities of human social interactions and language begs the question of how the brain processes the relevant incoming information and then generates responses so rapidly and effortlessly. Neurosurgeon Ziv Williams and his team at Harvard Medical School have made major advances in answering these questions. By recording the activities of hundreds of individual neurons in the brains of non-human primates in game-theory paradigms of social cooperation and conflict he has identified neurons in the prefrontal cortex that encode social agent identity. Moreover, by recording from neurons in the brains of human patients undergoing brain surgery his team has identified neurons involved in single elements of speech production or in the semantic encoding during language comprehension. These findings not only advance an understanding of the neurobiological underpinnings of social interactions and language, but also provide insight into disorders involving alterations in these processes.

LINKS

Dr. Williams Harvard webpage

https://zivwilliams.mgh.harvard.edu/

Neuronal circuits for social decision-making

https://pmc.ncbi.nlm.nih.gov/articles/PMC8517320/pdf/fnins-15-720294.pdf

Social agent identity cells in the prefrontal cortex of interacting groups of primates.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8571805/pdf/nihms-1752328.pdf

Single-neuronal predictions of others' beliefs in humans.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7990696/pdf/nihms-1654341.pdf

Single-neuronal elements of speech production in humans.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10866697/pdf/41586_2023_Article_6982.pdf

Semantic encoding during language comprehension at single-cell resolution.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11254762/pdf/41586_2024_Article_7643.pdf

One in seven people experience migraine headaches while others suffer with even more debilitating cluster headaches. The causes of these headaches are not fully understood and current treatments provide only partial relief. In this episode pharmacologist Antoinette van den Brink and neurologist Rolf Fronczek describe the clinical features of these headaches, the current understanding of their causes, and hormonal and environmental factors that can trigger the headaches. Drugs that inhibit the peptide CGRP and electrical stimulation of the occipital nerve are among treatments shown to be effective in reducing headache intensity or duration.

LINKS

University webpages:

https://www.erasmusmc.nl/en/research/researchers/maassen-van-den-brink-antoinette

https://hoofdpijnonderzoek.nl/en/team/dr-rolf-fronczek/

Migraine headache articles

https://journals.sagepub.com/doi/epub/10.1177/03331024241238153

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863119/pdf/10194_2024_Article_1724.pdf

Cluster headache articles

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018790/pdf/40263_2019_Article_696.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10755111/pdf/main.pdf

Consciousness is one’s awareness of electrochemically conveyed information coming into the brain from the environment via sensory pathways or generated within the brain’s neuronal networks (i.e., thoughts). In popular culture ‘consciousness’ is often portrayed as a mysterious concept or process. However, research that examines the effects of anesthetics, sleep, brain injuries, and psychedelics on neuronal network activity using fMRI, EEG and other technologies is revealing the circuits and activity patterns that enable consciousness. In this episode University of Cambridge Professor Andrea Luppi talks about his research on the neurochemical and neural network level underpinnings of consciousness. His integration of fMRI and brain connectome data suggest the importance of ‘gateway neuronal networks’ and ‘broadcasters’ (executive control networks) in human consciousness. We also discuss consciousness from philosophical and evolutionary perspectives.

LINKS

Professor Luppi’s profile at the University of Cambridge

https://neuroscience.cam.ac.uk/member/al857/

Recent review article on consciousness

https://www.cell.com/action/showPdf?pii=S0166-2236%2824%2900087-0

Gateway regions and broadcasters

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257694/pdf/elife-88173.pdf