Health depends upon proper regulation of circadian rhythms of cell and organ functions. Disruption of circadian rhythms has detrimental consequences for brain function and resilience and abnormal circadian rhythms are a common feature of Alzheimer’s disease. In this episode neurology professor Erik Musiek talks about the roles of specific circadian clock proteins in neurons and glial cells in brain health and Alzheimer’s disease. His research is revealing the ways in which these circadian regulatory proteins affect brain cell functions and how disruption of circadian rhythms may contribute to the neuropathological features of Alzheimer’s disease (amyloid plaques and neurofibrillary tangles. We also talk about ways in which we can bolster our circadian rhythms by sleep, exercise, diet, light exposure, etc.

LINKS

Professor Musiek’s webpage: https://physicians.wustl.edu/people/erik-musiek-md-phd/

Articles discussed in this podcast:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12352436/pdf/nihms-2097957.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11996435/pdf/nihpp-2025.03.31.645805v1.pdf

https://www.nature.com/articles/s43587-025-00950-x

https://pmc.ncbi.nlm.nih.gov/articles/PMC9008766/pdf/nihms-1794994.pdf

Chronic uncontrolled stress is a risk factor for many different diseases including mental and neurodegenerative disorders. The effects of such stress on the brain differ considerably between females and males. However, the vast majority of preclinical studies in animal models have included only males which in some cases has resulted in therapeutic interventions that are less effective in females compared to males. In this episode Georgia Hodes talks about sex differences in the effects of stress on the brain and neuroendocrine systems and how these differences can influence disease processes and treatments.

LINKS

Prof. Hodes webpage at VT:

https://neuroscience.vt.edu/our-people/research-faculty/hodes-georgia.html

Review articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10845083/pdf/CN-22-475.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10189838/pdf/nihms-1896436.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC8630768/pdf/nihms-1528739.pdf

In stressful situations the brain communicates with the adrenal glands stimulating them to release adrenaline and cortisol. This stress responsive neuroendocrine system plays important adaptive roles by regulating energy metabolism, attention, and learning and memory. However, without a recovery period chronic uncontrolled stress such as psychosocial stress can damage neural circuits in the brain and contribute to a range of mental disorders as well as Alzheimer’s disease. In this episode I have the pleasure of talking with two pioneers in the field of stress research – Professors Marian Joëls and Ron de Kloet. Their work which spans five decades has shown how two different cortisol receptors determine how the brain responds to physiological and pathological stress. They have revealed how a “cortisol switch” determines brain vulnerability or resilience.

Links

Marian Joëls’ webpage: https://www.rug.nl/staff/m.joels/cv

Ron de Kloet publications on Google Scholar: https://scholar.google.com/citations?user=Eao7yZIAAAAJ&hl=en&oi=ao

The “Cortisol Switch”

file:///Users/markmattson/Downloads/s41380-022-01934-8.pdf

https://www.sciencedirect.com/science/article/pii/S0091302218300116?via%3Dihub