Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain
Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain
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DOI：
10.1016/j.jsbmb.2006.12.096
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Feron, F.
中科院分区：
文献类型：
--
作者：
Eyles, D.;Almeras, L.;Feron, F.
流行病学强调了出生季节、纬度和多发性硬化症和精神分裂症等脑部疾病的流行之间的联系。根据这些数据，我们假设产前低维生素D的“印记”可能会导致这两种大脑疾病的风险。以前，我们已经表明，短暂的发育性维生素D缺乏症诱导成人神经系统的永久性变化。本研究的目的是检查产前维生素D缺乏症对成年大鼠大脑中基因表达的影响。缺乏维生素D的雌性大鼠与缺乏维生素D的雄性大鼠交配，并在出生后用对照饮食喂养后代。在第10周时，使用Affyssin基因微阵列将后代脑中的基因表达与对照动物进行比较。产前维生素D缺乏症导致几种生物学途径的显著失调，包括氧化磷酸化、氧化还原平衡、细胞骨架维持、钙稳态、陪伴、翻译后修饰、突触可塑性和神经传递。这些数据的计算分析表明，受损的突触网络可能是线粒体功能障碍的后果。由于线粒体代谢的破坏与多发性硬化症和精神分裂症有关，发育性维生素D缺乏症可能是研究这两种脑部疾病的启发性动物模型。(c)2006爱思唯尔有限公司保留所有权利。
Epidemiology has highlighted the links between season of birth, latitude and the prevalence of brain disorders such as multiple sclerosis and schizophrenia. In line with these data, we have hypothesized that 'imprinting' with low prenatal vitamin D could contribute to the risk of these two brain disorders. Previously, we have shown that transient developmental hypovitaminosis D induces permanent changes in adult nervous system. The aim of this study was to examine the impact of prenatal hypovitaminosis D on gene expression in the adult rat brain. Vitamin D deficient female rats were mated with undeprived males and the offspring were fed with a control diet after birth. At Week 10, gene expression in the progeny's brain was compared with control animals using Affymetrix gene microarrays. Prenatal hypovitaminosis D causes a dramatic dysregulation of several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, post-translational modifications, synaptic plasticity and neurotransmission. A computational analysis of these data suggests that impaired synaptic network may be a consequence of mitochondrial dysfunction. Since disruptions of mitochondrial metabolism have been associated with both multiple sclerosis and schizophrenia, developmental vitamin D deficiency may be a heuristic animal model for the study of these two brain diseases. (c) 2006 Elsevier Ltd. All rights reserved.