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我们能从动物模型中学到什么来研究精神分裂症?

What Can We Learn from Animal Models to Study Schizophrenia?

作者信息

Crunfli Fernanda, Brandão-Teles Caroline, Zuccoli Giuliana S, Chaves Filho Adriano J M, Vieira Gabriela Maciel, Silva-Amaral Danyelle, Crippa José Alexandre, Pedrazzi João F C, Macêdo Danielle S, Del-Bel Elaine, Gomes Felipe V

机构信息

Laboratory of Neuroproteomics, Department of Cell and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do Ceará, NPDM, Fortaleza, CE, Brazil.

出版信息

Adv Exp Med Biol. 2022;1400:15-33. doi: 10.1007/978-3-030-97182-3_2.

Abstract

Schizophrenia is a complex and heterogeneous neurodevelopmental psychiatric disorder characterized by a variety of symptoms classically grouped into three main domains: positive (hallucinations, delusions, and thought disorder) and negative symptoms (social withdrawal, lack of affect) and cognitive dysfunction (attention, working and episodic memory functions, and processing speed). This disorder places an immense emotional and economic pressure on the individual and society-at-large. Although the etiology of schizophrenia is not completely known, it is proposed to involve abnormalities in neurodevelopmental processes and dysregulation in the signaling mediated by several neurotransmitters, such as dopamine, glutamate, and GABA. Preclinical research using animal models are essential in our understanding of disease development and pathology as well as the discovery and advance of novel treatment choices. Here we describe rodent models for studying schizophrenia, including those based on the effects of drugs (pharmacological models), neurodevelopmental disruption, demyelination, and genetic alterations. The advantages and limitations of such models are highlighted. We also discussed the great potential of proteomic technologies in unraveling the molecular mechanism of schizophrenia through animal models.

摘要

精神分裂症是一种复杂的异质性神经发育性精神障碍,其特征是有多种症状,经典地分为三个主要领域:阳性症状(幻觉、妄想和思维紊乱)、阴性症状(社交退缩、情感缺乏)和认知功能障碍(注意力、工作和情景记忆功能以及处理速度)。这种疾病给个人和整个社会带来了巨大的情感和经济压力。虽然精神分裂症的病因尚不完全清楚,但据推测它涉及神经发育过程中的异常以及由几种神经递质(如多巴胺、谷氨酸和γ-氨基丁酸)介导的信号传导失调。使用动物模型的临床前研究对于我们理解疾病的发展和病理以及新治疗选择的发现和推进至关重要。在这里,我们描述用于研究精神分裂症的啮齿动物模型,包括基于药物作用的模型(药理学模型)、神经发育破坏、脱髓鞘和基因改变的模型。强调了这些模型的优点和局限性。我们还讨论了蛋白质组学技术通过动物模型揭示精神分裂症分子机制的巨大潜力。

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