Changes in the expression of the vitamin D receptor and LVSCC-A1C in the rat hippocampus submitted to single prolonged stress

Abstract

Abstract. Vitamin D signaling not only controls calcium (Ca 2+ ) and phosphorus uptake and transport, but also correlates with neurocognitive decline and neurodegenerative diseases. Almost all actions of Vitamin D are mediated by the transcription factor, vitamin D receptor (VDR), which has been widely identified in the central nervous system. Although previous studies have substantially advanced the understanding of the action of VDR in the brain, much remains unknown concerning how VDR relates to stress. Multiple lines of evidence indicate that the downregulation of L-type voltage-sensitive Ca 2+ -channels α-1C (LVSCC-A1C) by vitamin D in hippocampal neurons is able to reduce the influx and excitotoxic effects of Ca 2+ to neurons. Along these lines, the purpose of the present study was to analyze the relative expression of VDR in the hippocampus of rats exposed to single prolonged stress (SPS) as a putative animal model for human post-traumatic stress disorder (PTSD). Furthermore, changes in the levels of expression of LVSCC-A1C and Ca 2+ (neurotransmitter content) were examined during the onset periods of PTSD. The results revealed an increase in the expression of VDR at 1, 3 and 7 days post-stress compared with the control group. The intracellular free Ca 2+ levels in the hippocampus increased 1 day after SPS exposure, and then decreased gradually to the normal level at 14 days, consistent with the expression pattern of LVSCC-A1C. These results indicated that VDR may be involved in the pathogenesis of SPS rats, thereby providing an alternative preparation to search for optimal therapeutic strategies for PTSD. IntroductionPost-traumatic stress disorder (PTSD) is a severe anxiety disorder that may develop following exposure to any threat or injury that results in psychological trauma. Diagnostic symptoms for PTSD include re-experiencing the original trauma through flashbacks or nightmares, avoidance of stimuli associated with the trauma and increased arousal. Single-prolonged stress (SPS), an animal model of PTSD, has been extensively developed and employed in the investigation of PTSD (1-3). The three areas of the brain whose function may be altered in PTSD have been identified as the prefrontal cortex, the amygdala and the hippocampus, among which, the hippocampus is a key organ of the limbic system involved in learning and memory, as well as being a regulatory center for the stress response (4).Alterations in brain neurochemistry have been linked with neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, depression and cognitive decline. Previous studies have identified a positive association between vitamin D signaling and cognitive function (5). Vitamin D may regulate neurotransmission, neuroprotection and neuroimmunomodulation as a neurosteroid hormone (5,6), in addition to its critical role in calcium (Ca 2+ ) and phosphorous regulation and skeletal mineralization (7). Hypovitaminosis D is associated with several neuropsychiatric disorders, including dementia, Parkinson's d...

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