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P2–038: Unexpected impact of vitamin D deficiency: Disruption of vitamin D membrane receptor (1,25 MARRS) induces presenilin 1 expression
Author(s) -
GezenAk Duygu,
Dursun Erdinc,
Yilmazer Selma
Publication year - 2013
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.2013.05.680
Subject(s) - calcitriol receptor , vitamin d and neurology , endocrinology , medicine , vitamin d deficiency , biology , presenilin , glucocerebrosidase , alzheimer's disease , disease
Background: The deficiency or insufficiency of 25-hydroxyvitamin D 3 which is major circulating form of vitamin D was reported for individuals suffering from Alzheimer’s disease (AD), Parkinson’s disease (PD) or cognitive decline in recent studies. We showed that vitamin D receptor suppression is a part of beta amyloid (A b) pathology, vitamin D receptor silencing mimics the A b induced alterations and vitamin D supplementation to neurons rebalance the calcium channel alpha 1 C and nerve growth factor levels that are impaired with A b. We also showed that vitamin D receptor and 25hydroxyvitaminD 3 -24hydroxylase (24OHase) which is essential for vitamin D catabolism is expressed higher in hippocampus. We speculated this result as the “higher requirement of vitamin D” in hippocampus which might be more important for cognitive functions. The aim of this study was to investigate presenilin 1 (PSEN1), one of the important actors of AD type pathology in vitamin D nuclear receptor (VDR) or vitamin Dmembrane receptor (1,25 MARRS) silenced cortical neurons in order to test an evidence for the direct contribution of vitamin D deficiency or inefficient utilization of vitamin D to AD type pathology. Methods: Vitamin D-VDR pathway disruption model established by silencing VDR with corresponding siRNAs and vitamin D-1,25 MARRS pathway disrupted by utilizing 1,25 MARRS siRNAs in the primary cortical neuron cultures of Sprague Dawley rat embryos.The expressions of PSEN1, VDR and 1,25 MARRS, Cyclophilin B were studied with qRT-PCR and Western blotting. Results: PSEN1 expression was significantly higher in 1,25MARRS silenced cortical neurons compared to control, vehicle, non target siRNA, or cyclophilin B siRNA treated neurons (p<0.05, p<0.01, p<0.01, p<0.05, respectively). Although there was a slight increase in the PSEN1 expression of VDR silenced cortical neurons; this elevation was not statistically significant. The results confirmed with western blotting. Conclusions: Our results indicate for the first time that vitamin D pathway impairment has a direct effect on one of the important components of gamma secretase complex, the presenilin 1. Thus vitamin D supplementation should be seriously considered as a candidate molecule both in treatment and prevention of AD.