Dose Paradox: Low Dose Can Be Worse

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Genetic & environmental factors that affect brain health, including why people age faster in outer space. (Note: technical difficulties affected the audio quality of this recording somewhat)

Episode Summary: Dr. Jacob Raber explains how apolipoproteins, particularly ApoE, influence brain health and disease risk; their role in cholesterol metabolism, Alzheimer’s disease, and responses to environmental stressors like radiation and viral infections; interplay between genetics, diet, and lifestyle factors, highlighting how these affect cognitive function and resilience to stress; research into space radiation, the gut-brain axis, and potential interventions for neurodegenerative diseases.

About the guest: Jacob Raber, PhD, is a neuroscientist at Oregon Health & Science University (OHSU) in Portland, where he leads a lab studying genetic and environmental influences on brain health, particularly using mouse models with human genes.

Discussion Points:

• Apolipoproteins (ApoE2, E3, E4) are proteins involved in cholesterol and lipid metabolism in the brain, with ApoE4 increasing risks for Alzheimer’s and cardiovascular disease.
• ApoE4 carriers may face higher risks for cognitive decline but could have advantages in specific contexts, like fertility or certain infections.
• Environmental stressors, such as space radiation and viral infections like West Nile, can exacerbate oxidative stress, impacting brain health.
• The gut microbiome influences brain function indirectly via the gut-liver-brain axis, with ongoing studies exploring its role in Alzheimer’s and traumatic brain injury.
• Lifestyle factors like diet, exercise, and sleep are critical for brain health, potentially mitigating genetic risks like ApoE4.
• Statins, commonly used for cholesterol management, may impair learning in healthy animals, suggesting context-dependent effects.
• Research into space radiation reveals potential therapeutic applications, such as using heavy ion radiation for cancer treatment.
• Genetic variations, including ethnicity and sex, influence ApoE-related disease risks, with women and certain populations showing higher Alzheimer’s susceptibility.
• Chronic low-level stressors, like air pollution, may pose greater risks to brain health than acute exposures due to insufficient activation of protective mechanisms.

Related content:

• M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet

*Not medical advice

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