Lentiviral delivery of human wild-type Tau protein mediates a slow and progressive spatio-temporal Tau pathology in rat brain (original) (raw)

2011, Alzheimer's & Dementia

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, 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 Aß toxicity, it is possible to explain some of the events that occur during neurodegeneration.