Olde Loohuis Nikkie F M, Martens Gerard J M, van Bokhoven Hans, Kaplan Barry B, Homberg Judith R, Aschrafi Armaz
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 3;77:128-132. doi: 10.1016/j.pnpbp.2017.04.009. Epub 2017 Apr 10.
Autism spectrum disorders (ASD) are a highly heterogeneous group of neurodevelopmental disorders caused by complex interplay between various genes and environmental factors during embryonic development. Changes at the molecular, cellular and neuroanatomical levels are especially evident in the medial prefrontal cortex (mPFC) of ASD patients and are particularly contributing to social impairments. In the present study we tested the hypothesis that altered neuronal development and plasticity, as seen in the mPFC of ASD individuals, may result from aberrant expression of functionally connected genes. Towards this end, we combined transcriptome sequencing and computational gene ontology analysis to identify the molecular networks impaired in the mPFC of a valproic acid (VPA) rat model of autism. This investigation identified two subsets of genes differentially expressed in the mPFC of VPA rats: one group of genes being functionally involved in the regulation of the circadian rhythm, while the second group encompasses a set of differentially expressed collagen genes acting within the extracellular matrix. Ultimately, our integrated transcriptome analysis identified a distinct subset of altered gene networks in the mPFC of VPA rats, contributing to our understanding of autism at the molecular level, thus providing novel insight into the genetic alterations associated with this neurodevelopmental disorder.
自闭症谱系障碍（ASD）是一组高度异质性的神经发育障碍，由胚胎发育过程中各种基因与环境因素之间的复杂相互作用引起。分子、细胞和神经解剖学水平的变化在ASD患者的内侧前额叶皮质（mPFC）中尤为明显，并且对社交障碍有特别的影响。在本研究中，我们检验了这样一个假设：如在ASD个体的mPFC中所见，神经元发育和可塑性的改变可能源于功能连接基因的异常表达。为此，我们结合转录组测序和计算基因本体分析，以识别自闭症丙戊酸（VPA）大鼠模型的mPFC中受损的分子网络。这项研究确定了在VPA大鼠的mPFC中差异表达的两个基因子集：一组基因在功能上参与昼夜节律的调节，而第二组包括一组在细胞外基质中起作用的差异表达胶原蛋白基因。最终，我们的综合转录组分析确定了VPA大鼠mPFC中一组不同的基因网络改变，有助于我们在分子水平上理解自闭症，从而为与这种神经发育障碍相关的基因改变提供了新的见解。
