148. 1,25-Dihydroxycholecalciferol & The Brain | Forms of Vitamin D, Activation to 1,25-Dihydroxycholecalciferol, Mechanisms of Action / Neuroprotective Effects of Vitamin D, Cognitive Symptoms
In this episode, we explore the role of Vitamin D in brain health, focusing on how its active form, calcitriol (1,25-dihydroxyvitamin D3), influences cognitive function and neuroprotection. We’ll discuss the synthesis of Vitamin D, its conversion into its active form, and its ability to cross the blood-brain barrier to exert effects on neurons and glial cells. Additionally, we will highlight how calcitriol regulates gene expression through Vitamin D Response Elements (VDREs), impacting inflammation, antioxidant defense, and neurotrophic support. Finally, we touch on the symptoms of low Vitamin D and the link to cognitive decline. Topics: 1. Introduction to Vitamin D and the Brain - Forms of Vitamin D, synthesis, conversion/activation, and its role in the brain 2. Vitamin D - Vitamin D2 (ergocalciferol), plant-based sources like mushrooms - Vitamin D3 (cholecalciferol), UVB radiation, animal-based foods - Inactive forms 3. Synthesis and Conversion of Vitamin D3 - Synthesis in the skin: 7-dehydrocholesterol converts to pre-vitamin D3 - Conversion in the liver: 25-hydroxylase converts D3 to 25-hydroxyvitamin D (calcidiol) - Final activation in the kidneys: 1-alpha-hydroxylase converts calcidiol to 1,25-dihydroxycholecalciferol (calcitriol), the active form 4. Calcitriol and the Blood-Brain Barrier - Calcitriol’s lipophilic nature, crossing the BBB - The structure and function of the blood-brain barrier - How calcitriol diffuses across the BBB and reaches brain cells 5. Calcitriol's Role in the Brain - Interaction with Vitamin D receptors (VDRs) in neurons and glial cells - VDRs in key brain regions: hippocampus, prefrontal cortex, cerebellum, basal ganglia - Binding of calcitriol to VDRs, conformational change, and formation of the VDR-RXR complex 6. Gene Regulation via Vitamin D Response Elements (VDREs) - Overview of VDREs in promoter regions of genes - Role of calcitriol in activating or repressing gene transcription 7. Impact on Inflammatory Responses - VDREs in anti-inflammatory genes promote IL-10 expression - Calcitriol’s role in reducing pro-inflammatory cytokines like IL-6 and TNF-alpha 8. Neurotrophic Factors - VDREs’ role in regulating genes that promote BDNF - BDNF’s impact on neuron survival, growth, and synaptic connectivity 9. Antioxidant Enzymes - VDREs influence the expression of glutathione peroxidase and superoxide dismutase (SOD) - The role of these enzymes in defending neurons from oxidative stress 10. Brain Regions & Calcitriol - Hippocampus: Learning, memory, neurogenesis, synaptic plasticity - Prefrontal Cortex: Executive functions, mood regulation - Cerebellum: Motor control, cognitive processing, calcium homeostasis - Basal Ganglia: Movement regulation, protection of dopaminergic neurons - Amygdala: Emotion processing, fear, anxiety, stress response 11. Interconnection of Brain Regions - How Vitamin D’s effects on neurotransmitter regulation, anti-inflammatory action, and calcium homeostasis create a global protective effect. 12. Conclusion - Recap of calcitriol’s cellular mechanisms and neuroprotective effects - Symptoms of low Vitamin D Thank you to our episode sponsor: 1. Check out Daily Nouri and use code CHLOE20 for 20% off your order. Thanks for tuning in! Get Chloe's Book Today! "75 Gut-Healing Strategies & Biohacks" Follow Chloe on Instagram @synthesisofwellness Follow Chloe on TikTok @chloe_c_porter Visit synthesisofwellness.com to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support