the effects of vitamin d receptor silencing on the expression of lvscc-a1c and lvscc-a1d and the release of ngf in cortical neurons的影响维生素d受体表达的沉默lvscc-a1c lvscc-a1d和皮质神经元中神经生长因子的释放.pdf

The Effects of Vitamin D Receptor Silencing on the Expression of LVSCC-A1C and LVSCC-A1D and the Release of NGF in Cortical Neurons Duygu Gezen-Ak, Erdinc¸ Dursun, Selma Yilmazer* Istanbul University, Cerrahpasa Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey Abstract Background: Recent studies have suggested that vitamin D can act on cells in the nervous system. Associations between polymorphisms in the vitamin D receptor (VDR), age- dependent cognitive decline, and insufficient serum 25 hydroxyvitamin D3 levels in Alzheimer’s patients and elderly people with cognitive decline have been reported. We have previously shown that amyloid b (Ab) treatment eliminates VDR protein in cortical neurons. These results suggest a potential role for vitamin D and vitamin D-mediated mechanisms in Alzheimer’s disease (AD) and neurodegeneration. Vitamin D 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 expression levels and NGF release in VDR-silenced primary cortical neurons prepared from Sprague-Dawley rat embryos. Methodology/Principal Findings: qRT-PCR and western blots were performed to determine VDR, LVSCC-A1C and -A1D expression levels. NGF and cytotoxicity levels were determined by ELISA. Apoptosis was determined by TUNEL. Our findings illustrate that LVSCC-A1C mRNA and protein levels increased rapidly in cortical neurons when VDR is down-regulated, whereas, LVSCC-A1D mRNA and protein