精神分裂症实验模型综述

B. Naz, Prabhat Singh, Simon Nyarko, Ramzan Ali Banjara
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摘要

精神分裂症是一种严重的精神疾病,在大多数研究人群中终生患病率为1%。精神分裂症的神经病理学和精神病理学仍然知之甚少。这是由于缺乏足够的动物模型。精神分裂症是人类大脑的一种紊乱。因此,精神分裂症研究中动物模型的效力仅限于该疾病的某些方面。在动物中建立精神分裂症模型的最困难的方面之一是缺乏这种疾病的清晰和明确的概念框架。本文综述了氯胺酮(NMDA受体拮抗剂)、苯环利定(NMDA受体拮抗剂)等药物诱导的精神分裂症动物模型。讨论了精神分裂症的遗传动物模型,包括但不限于精神分裂症易感基因、神经调节蛋白-1(NRG1)、DAT基因、锌指DHH-type3 containing 8 (ZDHHC8)和Dysbindin。它进一步讨论了胎儿模型精神分裂症,断奶后的社会隔离,并以体外动物模型结束。使用动物模型来提高对促成精神分裂症发展的神经化学和中枢神经系统结构变化的理解,而不是专注于治疗症状,是开发新的更有效治疗策略的先决条件。由于精神分裂症病因学中基因-基因和基因-环境相互作用的复杂性和模糊性,开发更可靠的预测这种疾病的动物模型的挑战仍在进行中,最有可能通过多种早期生活干预。
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Review of Experimental Models of Schizophrenia
Schizophrenia is a severe psychiatric disease that has a lifetime prevalence of 1% in most of the populations studied. The neuropathology and psychopathology of Schizophrenia are still poorly understood. This is attributed to the paucity of adequate animal models. Schizophrenia is a disorder of the human brain. Consequently, the potency of animal models in Schizophrenia research is limited to certain aspects of the disease. One of the most difficult aspects of modelling Schizophrenia in animals has been the lack of a clear and explicit conceptual framework for this disorder. This review discussed drug-induced animal models of Schizophrenia such as Ketamine (NMDA receptor antagonist), Phencyclidine (NMDA receptor antagonist) etc. It also discussed genetic animal models of Schizophrenia which include but not limited to Schizophrenia susceptibility Genes, Neuregulin-1(NRG1), DAT gene, Zinc finger DHH-type3 containing 8 (ZDHHC8) and Dysbindin. It went further to discuss fetal models Schizophrenia, postweaning social isolation and ended with In-Vitro animal models. The use of animal models to improve understanding of the neurochemical and structural CNS changes that precipitate development of Schizophrenia, rather than a focus on treating the symptoms, is a prerequisite to enable new more effective therapeutic strategies to be developed. Because of the complexity and ambiguity of gene-gene and gene-environment interactions in the aetiology of schizophrenia, the challenge of developing more reliable predictive animal models of this disorder, most likely through multiple early-life interventions, is still ongoing.
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