Developmental vitamin D deficiency causes abnormal brain development.
Developmental vitamin D deficiency causes abnormal brain development.
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DOI：
10.1016/j.psyneuen.2009.04.015
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发表时间：
2009-12-01
影响因子：
3.7
通讯作者：
Burne, T H J
中科院分区：
文献类型：
--
作者：
Eyles, D W;Feron, F;Burne, T H J
现在有明确的证据表明维生素D参与大脑发育。我们的团队对塑造大脑发育的环境因素以及这与包括精神分裂症在内的神经精神疾病的关系感兴趣。精神分裂症的起源被认为是发育性的。我们假设发育性维生素D（DVD）缺乏可能是精神分裂症的几个重要流行病学相关因素的合理神经生物学解释，即：（1）冬季/春季出生率过高，（2）第二代非洲-加勒比移民发病率增加，（3）城市出生率增加。此外，我们已经发表了两篇直接的流行病学支持这一假设的患者。为了证实这一假说的“生物学合理性”，我们建立了一个动物模型来研究DVD缺乏对脑发育的影响。我们通过在繁殖前从雌性大鼠的饮食中去除维生素D来做到这一点。在出生时，我们将所有母鼠恢复到含有维生素D的饮食。使用这个程序，我们施加一个短暂的，妊娠期维生素D缺乏症，同时保持正常的钙水平。DVD缺陷母鼠后代的脑特征为（1）脑形状轻度变形，（2）侧脑室体积增加，（3）分化减少和（4）神经营养因子表达减少。成年后，脑室容积的改变持续存在，大脑基因和蛋白质表达的改变出现。成年DVD缺陷大鼠也表现出对诱发精神病的药物（NMDA拮抗剂MK-801）的行为敏感性，并在注意力处理方面存在障碍。在这篇综述中，我们总结了文献解决的功能，维生素D对神经元和非神经元细胞，以及在体内的结果，从DVD缺陷的动物。我们从这些数据中得出的结论是，维生素D是神经精神疾病的一个合理的生物风险因素，维生素D作为一种神经类固醇对大脑发育有直接影响。
There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that vitamin D acts as a neurosteroid with direct effects on brain development.