Poly I:C母体免疫刺激诱导的子代精神分裂症神经发育动物模型研究

摘要： 精神分裂症是一组病因未明的重性精神障碍，其病理生理学机制极其复杂，建立能够确切模拟精神分裂症的动物模型对于其发病机制的研究及抗精神分裂症药物的研发具有十分重要的意义。本文意在介绍产前母体免疫刺激（聚肌胞苷酸聚肌苷酸-聚胞苷酸，poly-I:C）诱导子代出现精神分裂症样的神经发育动物模型，以及该模型对精神分裂症的病因研究、生物学机制及其治疗和药物研发的重要意义。
Abstract: Human epidemiological studies have provided compelling evidence that the risk of developing schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behavior in later life. Based on these associations, developing a reliable, predictive animal model of psychiatric disorder, such as schizophrenia, is essential for us to study the neurobiological mechanisms and for the development of novel drugs with improved therapeutic efficacy. Therefore the goal of the article was to review the contribution of prenatal immune challenge (PIC) in pregnant rodent models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C) to the study of etiology, biological basis and treatment of schizophrenia. Available web databases (PubMed and ISI web of science) for original studies published in the last 10 years (From 2003 to 2013) concerning animal model of PIC, focusing on inducing by poly-I:C were searched in the article. The neurodevelopmental model, challenged by the viral mimetic poly-I:C, not only exerts behavioral effects on sensorimotor gating deficits, latent inhibition disruption, impaired object recognition memory and social behavior dysfunction in adult rat offspring, but further produces effects of postpubertal emergence of enhanced sensitivity to MK-801 and amphetamine-induced hyperlocomotion, all those effects are followed with morphofunctional alterations in the hippocampus and the entorhinal cortex in adult offspring. Several gene expression changes related to the developmental course of dopaminergic neurons, including the sonic hedgehog (ShhN) and fibroblastic growth factor 8 (FGF-8), as well as transcription factors like nuclear receptor related 1 protein (Nurr1) and pituitary homeobox 3 (Pitx3) can also be confirmed in the neurodevelopmental model. The ShhN and FGF-8 genes, as well as the transcription factors Nurr1 and Pitx3, are essential for the generation, differentiation, and maintenance of midbrain dopamine (DA) cells during embryonic development. Besides that, chronic injection of antipsychotics (haloperidol and clozapine) or the antidepressant fluoxetine during periadolescence