Additional Clues for a Protective Role ofVitamin D in Neurodegenerative Diseases: 1,25-Dihydroxyvitamin D3 Triggers an Anti-Inflammatory Response in BrainPericytes
Abstract
Epidemiological and experimental studies suggest that 1,25-dihydroxyvitamin D3 (1,25D) plays a neuroprotectiverole in neurodegenerative diseases including Alzheimer's disease. Most of the experimental data regarding the genes regulatedby this hormone in brain cells have been obtained with neuron and glial cells. Pericytes play a critical role in brain function thatencompasses their classical function in blood-brain barrier control and maintenance. However, the gene response of brain pericyteto 1,25D remains to be investigated. Analyses of the transcriptomic response of human brain pericytes to 1,25D demonstrate thathuman brain pericytes in culture respond to 1,25D by regulating genes involved in the control of neuroinflammation. In addition,ericytes respond to the pro-inflammatory cytokines tumor necrosis factor and Interferon by inducing the expression of theCYP27B1 gene which is involved in 1,25D synthesis. Taken together, these results suggest that neuroinflammation could triggerthe synthesis of 1,25D by brain pericytes, which in turn respond to the hormone by a global anti-inflammatory response. Thesefindings identify brain pericytes as a novel 1,25D-responsive cell type and provide additional evidence for the potential value ofvitamin D in the prevention or therapy of Alzheimer's disease and other neurodegenerative/neuropsychiatric diseases associatedwith an inflammatory component.
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