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P1‐040: Early changes of cholinergic receptors in hippocampus and parietotemporal cortex of the rat model of sporadic Alzheimer's disease
Author(s) -
Knezovic Ana,
SalkovicPetrisic Melita
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.320
Subject(s) - muscarinic acetylcholine receptor , medicine , endocrinology , hippocampus , cholinergic , streptozotocin , nicotinic agonist , receptor , muscarinic acetylcholine receptor m1 , neurochemical , muscarinic acetylcholine receptor m4 , cortex (anatomy) , biology , neuroscience , diabetes mellitus
disease (AD) and neurodegeneration. VitaminD has been shown to down-regulate the L-type voltage-sensitive calcium channels, LVSCC-A1C and LVSCC-A1D, and up-regulate (nerve growth factor) NGF. However, expression of these proteins when VDR is repressed is unknown. The aim of this study is to investigate LVSCC-A1C, LVSCC-A1D, calbindin-D28k, inducible nitric oxide synthase (iNOS) expressions and NGF release in VDR-silenced primary cortical neurons. Methods: qRT-PCR and western blots were performed to determine VDR, LVSCC-A1C, LVSCC-A1D, calbindin-D28k and iNOS expression levels. NGF and cytotoxicity levels were determined by ELISA. Apoptosis was determined by TUNEL. Results: Our findings illustrate that LVSCC-A1C and iNOS expressions increased rapidly in cortical neurons when VDR is down-regulated, whereas, LVSCC-A1D levels did not change, NGF release calbindin-D28k expression decreased in response to VDR down-regulation. Although vitamin D regulates LVSCC-A1C through VDR, it may not regulate LVSCC-A1D through VDR. Conclusions: Our results indicate that suppression of VDR or vitamin D-VDR pathway disruption disrupts LVSCC-A1C, calbindin-D28k and NGF production and increase oxidative stress. Thus it can make neurons vulnerable to aging and neurodegeneration, and when combined with As toxicity, it is possible to explain some of the events that occur during neurodegeneration.