Queensland Brain Institute, University of Queensland, Qld 4072, Australia.
Neurosci Lett. 2010 Dec 17;486(3):220-3. doi: 10.1016/j.neulet.2010.09.057. Epub 2010 Sep 25.
Schizophrenia is a neurodevelopment disorder that is strongly associated with alterations in dopamine neurotransmission. Common features of animal models of schizophrenia include behavioural, cognitive and/or pharmacological abnormalities reflective of aberrant DA signaling. The aim of this study was to examine the expression of genes important for dopaminergic development and maturation within the embryonic mesencephalon using an epidemiologically-informed animal model of schizophrenia, the developmental vitamin D (DVD) deficient rat model. Two groups of female Sprague-Dawley rats were fed either a diet replete (1000IU/kg) or deplete (0IU/kg) of vitamin D, mated and foetal mesencephalon collected at embryonic day (E) E12 or E15. Using real time-PCR, the DVD-deficient embryos had a significant reduction in factors crucial in specifying dopaminergic phenotype, such as Nurr1 and p57Kip2. No group differences were found for Lmx1b or Ptx3. Reductions in these specification factors may alter the ontogeny of DA neurons and may ultimately help to explain the behavioural abnormalities reported in adult offspring from this model.
精神分裂症是一种神经发育障碍,与多巴胺神经传递的改变密切相关。精神分裂症动物模型的常见特征包括行为、认知和/或药理学异常,反映出异常的 DA 信号。本研究旨在使用一种具有流行病学意义的精神分裂症动物模型,即发育性维生素 D(DVD)缺乏大鼠模型,研究胚胎中脑内多巴胺能发育和成熟相关基因的表达。两组雌性 Sprague-Dawley 大鼠分别喂食富含(1000IU/kg)或缺乏(0IU/kg)维生素 D 的饮食,交配并在胚胎第 12 天(E12)或第 15 天(E15)收集胎脑中脑。实时 PCR 结果显示,DVD 缺乏的胚胎中,对多巴胺能表型具有关键作用的因子,如 Nurr1 和 p57Kip2 的表达显著减少。Lmx1b 或 Ptx3 两组间无差异。这些调节因子的减少可能会改变 DA 神经元的发育,并最终有助于解释该模型成年后代报告的行为异常。