Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249

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Cellular clean up by immune cells and how early-life fructose exposure leads to neurodevelopmental problems.

Episode Summary: Dr. Justin Perry talks about the body's constant cellular turnover—about 3 million cells die per second in adults (double in children and women)—handled by phagocytes like macrophages that engulf and digest debris to prevent diseases like lupus. They explore phagocytosis steps, macrophage adaptations in tissues like the brain (microglia), and how high fructose intake impairs microglial function in developing mice, leading to uncleared brain cells and anxiety-like behaviors, with implications for human neurodevelopmental disorders amid rising fructose consumption.

About the guest: Justin Perry, PhD is an immunologist and clinical psychologist who leads a lab at Memorial Sloan Kettering Cancer Center focusing on how the body clears dead cells and debris to maintain homeostasis.

Discussion Points:

• The body turns over 1-2% of its 30 trillion cells daily, mostly blood cells, but neurons in kids and endometrium in women turnover at ~2x this rate
• Phagocytosis involves "find me," "eat me," and digestion signals; failures can cause autoimmunity.
• Microglia are brain macrophages that uptake fructose via GLUT5 transporter.
• Early high fructose exposure (comparable to one soda daily) impairs the pruning of synapses and dead neurons.
• In mice, prenatal or postnatal fructose causes phagocytosis deficits in the prefrontal cortex, leading to heightened fear responses and poor fear extinction, mimicking anxiety disorders.
• Fructose correlates with rising neurodevelopmental issues like autism and anxiety; it's passed via breast milk, and liquid forms (e.g., sodas) overwhelm metabolic shields more than solid fruits.
• Macrophages may hold keys to diseases from atherosclerosis to cancer; deleting GLUT5 in microglia reverses fructose's effects, hinting at evolutionary roles in aging or low-oxygen states.

Related content:

• M&M 215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary Patti
• Article | Dietary Fructose & Metabolic Health: An Evolutionary Perspective

Reference Paper:

• Study | Early life high fructose impairs microglial phagocytosis and neurodevelopment

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