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PNAS:揭示与孤独症和精神分裂症相关的动态基因网络

PNAS:揭示与孤独症和精神分裂症相关的动态基因网络

英国科学家公布的一项针对小鼠的精神及心理疾病研究新成果,研究发现与自闭症和精神分裂症有关的基因,只活跃于大脑发育的早期阶段。相关研究结果发表在美国《国家科学院学报》(PNAS)上。

研究小组对小鼠大脑发育过程中的基因表达情况进行了研究,这一发育过程从15天的小鼠胚胎开始,一直到小鼠成年期结束。结果研究人员发现,与自闭症和精神分裂症有关的基因,只会在小鼠大脑发育的特定阶段才活跃于大脑的“基底板”(subplate)部位。

研究人员表示,大部分自闭症易感基因仅在小鼠大脑发育阶段才会在大脑基底板部位表达,而多数基因只能在特定的大脑发育阶段才会被发现,而随后就很难再被确认。

对于大脑皮层的发育是否会由于基因异常或环境压力(如早产)而被破坏,进而影响大脑发育并导致多动症和自闭症等疾病,学界长期以来一直未有定论。而新研究对可能导致自闭症和精神分裂症的基因在小鼠大脑发育特定阶段的活动进行了定义,表明大脑早期发育情况异常是引起这类神经心理问题的重要原因之一。而对于这类常见遗传因素的了解,则有助于科学家对大脑发育的整体研究更上一层楼。

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Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia

PNAS, February 11, 2013 | doi:10.1073/pnas.1218510110

The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/. We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders.

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