Zhang Kexuan, Liao Panlin, Wen Jin, Hu Zhonghua
Hunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410008, Hunan, PR China.
IBRO Neurosci Rep. 2023 Feb 4;14:244-252. doi: 10.1016/j.ibneur.2023.01.008. eCollection 2023 Jun.
Schizophrenia is a severe neuropsychiatric syndrome with psychotic behavioral abnormalities and marked cognitive deficits. It is widely accepted that genetic and environmental factors contribute to the onset of schizophrenia. However, the etiology and pathology of the disease remain largely unexplored. Recently, the synaptopathology and the dysregulated synaptic plasticity and function have emerging as intriguing and prominent biological mechanisms of schizophrenia pathogenesis. Synaptic plasticity is the ability of neurons to change the strength of their connections in response to internal or external stimuli, which is essential for brain development and function, learning and memory, and vast majority of behavior responses relevant to psychiatric diseases including schizophrenia. Here, we reviewed molecular and cellular mechanisms of the multiple forms synaptic plasticity, and the functional regulations of schizophrenia-risk factors including disease susceptible genes and environmental alterations on synaptic plasticity and animal behavior. Recent genome-wide association studies have provided fruitful findings of hundreds of risk gene variances associated with schizophrenia, thus further clarifying the role of these disease-risk genes in synaptic transmission and plasticity will be beneficial to advance our understanding of schizophrenia pathology, as well as the molecular mechanism of synaptic plasticity.
精神分裂症是一种严重的神经精神综合征，伴有精神病性的行为异常和明显的认知缺陷。遗传和环境因素导致精神分裂症的发病，这一点已被广泛接受。然而，该疾病的病因和病理在很大程度上仍未得到充分探索。最近，突触病理学以及失调的突触可塑性和功能已成为精神分裂症发病机制中引人关注且突出的生物学机制。突触可塑性是指神经元响应内部或外部刺激改变其连接强度的能力，这对于大脑发育和功能、学习和记忆以及绝大多数与包括精神分裂症在内的精神疾病相关的行为反应至关重要。在此，我们综述了多种形式突触可塑性的分子和细胞机制，以及精神分裂症风险因素（包括疾病易感基因和环境改变）对突触可塑性和动物行为的功能调节。最近的全基因组关联研究已经获得了数百个与精神分裂症相关的风险基因变异的丰硕研究结果，因此进一步阐明这些疾病风险基因在突触传递和可塑性中的作用，将有助于增进我们对精神分裂症病理学以及突触可塑性分子机制的理解。
