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理解精神分裂症的转化研究:动物模型的新视角。

Understanding translational research in schizophrenia: A novel insight into animal models.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Guwahati, India.

Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar, India.

出版信息

Mol Biol Rep. 2023 Apr;50(4):3767-3785. doi: 10.1007/s11033-023-08241-7. Epub 2023 Jan 24.

Abstract

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.

摘要

精神分裂症影响着全球数百万人,是科学界面临的主要挑战。与大多数精神病一样,它也被认为是一种由神经递质失衡引起的复杂精神障碍。由于神经病理学的复杂性,它始终是一种复杂的疾病。由于对病理生理学缺乏适当的理解,使得这种疾病在临床环境中难以治疗。然而,由于最近在动物模型方面的进展,我们希望在临床环境中能够有更好的治疗方法,并取得更多的成功。多巴胺、谷氨酸、GABA 和血清素是参与精神分裂症病理生理学的神经递质。已经提出了各种基于这些神经递质的动物模型,包括药理学、神经发育和遗传模型。精神分裂症也报道了神经结合蛋白、DICS1 和 NRG1 等基因的多态性。基于多巴胺、谷氨酸和血清素的假说被认为是精神分裂症的成功模型,迄今为止,已经针对这些模型设计了药物治疗方法。新的靶点,如食欲素系统、毒蕈碱和烟碱受体以及大麻素受体,已被用于减轻阴性和认知症状。非药理学模型,如断奶后社会隔离模型(母婴分离)、隔离饲养模型等,也被开发出来以模拟精神分裂症的症状,并创造和测试新的药物治疗方法,这是目前精神疾病的一个突破。在这些特定模型中已经评估了不同的行为测试。这篇综述将重点介绍目前可用于精神障碍(包括精神分裂症)的动物模型和行为测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbad/10042983/771f95f68e30/11033_2023_8241_Fig1_HTML.jpg

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