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Chronic vitamin D 3 treatment protects against neurotoxicity by glutamate in association with upregulation of vitamin D receptor mRNA expression in cultured rat cortical neurons
Author(s) -
Taniura Hideo,
Ito Minoru,
Sanada Noriko,
Kuramoto Nobuyuki,
Ohno Yu,
Nakamichi Noritaka,
Yoneda Yukio
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20824
Subject(s) - calcitriol receptor , medicine , biology , endocrinology , downregulation and upregulation , cerebral cortex , glutamate receptor , cerebellum , neurotoxicity , in situ hybridization , vitamin d and neurology , gene expression , receptor , biochemistry , gene , toxicity
The vitamin D receptor (VDR) is believed to mediate different biologic actions of vitamin D 3 , an active metabolite of vitamin D, through regulation of gene expression after binding to specific DNA‐response element (VDRE) on target genes. To further understand roles of both vitamin D 3 and VDR in the central nervous system, we examined VDRE binding in nuclear extracts prepared from discrete rat brain regions and cultured rat cortical neurons by electrophoretic mobility shift assay. The highest activity of VDRE binding was found in the cerebellum among other brain regions examined, but sequence specific by taking into consideration the efficient competition with excess unlabeled VDRE but not with mutated VDRE. On in situ hybridization analysis, cells stained for VDR mRNA were abundant in neuron‐enriched areas of cerebral cortex, hippocampus and cerebellar cortex in the mouse brain. Chronic treatment of vitamin D 3 increased the expression of microtubule‐associated protein‐2, growth‐associated protein‐43 and synapsin‐1 in cultured rat cortical neurons, suggesting a trophic role of vitamin D 3 in differentiation and maturation of neurons. Neuronal cell death by brief glutamate exposure was significantly protected in cultured cortical neurons chronically treated with vitamin D 3 . Parallel studies showed that VDR mRNA was significantly upregulated 12–24 hr after brief glutamate exposure in cultured neurons chronically treated with vitamin D 3 , but not in those with vehicle alone. Our results suggest that vitamin D 3 may play a role in mechanisms relevant to protective properties against the neurotoxicity of glutamate through upregulation of VDR expression in cultured rat cortical neurons. © 2006 Wiley‐Liss, Inc.