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精神障碍遗传和染色体变异的啮齿动物模型。

Rodent models of genetic and chromosomal variations in psychiatric disorders.

机构信息

RIKEN Brain Science Institute, Saitama, Japan.

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, USA.

出版信息

Psychiatry Clin Neurosci. 2017 Aug;71(8):508-517. doi: 10.1111/pcn.12524. Epub 2017 Apr 23.

Abstract

Elucidating the molecular basis of complex human psychiatric disorders is challenging due to the multitude of factors that underpin these disorders. Genetic and chromosomal changes are two factors that have been suggested to be involved in psychiatric disorders. Indeed, numerous risk loci have been identified in autism spectrum disorders, schizophrenia, and related psychiatric disorders. Here, we introduce genetic animal models that disturb excitatory-inhibitory balance in the brain and animal models mirroring human chromosomal abnormalities, both of which may be implicated in autism spectrum disorder pathophysiology. In addition, we discuss recent unique translational research using rodent models, such as Cntnap2 knockout mouse, Mecp2 mutant mouse, Pick1 knockout mouse, and neonatal ventral hippocampal lesion rat. By using these models, several types of drugs are administered during the developmental period to see the effect on psychotic symptoms and neural activities in adults. The accumulating evidence from recent animal studies provides an informative intervention strategy as a translational research.

摘要

由于影响精神疾病的因素众多,阐明其发病的分子基础极具挑战性。遗传和染色体变化是与精神疾病相关的两个因素。事实上,已经在自闭症谱系障碍、精神分裂症和相关精神疾病中鉴定出了许多风险基因座。在这里,我们介绍了扰乱大脑中兴奋-抑制平衡的遗传动物模型,以及模拟人类染色体异常的动物模型,这些都可能与自闭症谱系障碍的病理生理学有关。此外,我们还讨论了最近使用啮齿动物模型(如 Cntnap2 敲除鼠、Mecp2 突变鼠、Pick1 敲除鼠和新生海马损伤大鼠)进行的独特转化研究。通过使用这些模型,在发育期间给予多种类型的药物,观察其对成年后精神症状和神经活动的影响。最近的动物研究积累的证据为转化研究提供了一种有信息的干预策略。

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