The function and mechanism of GABAergic signaling in schizophrenia

研究提供了精神分裂症中GABA能系统异常的证据。大麻素受体可能在调节GABA能神经元中起作用。本研究对精神分裂症病理生理中的GABA能神经传递和大麻素途径进行了遗传学分析，探讨了精神分裂症发病与遗传变异的关系，以及精神分裂症患者死后脑组织中基因表达的变化。我们发现这些信号通路中的许多基因与疾病有关。此外，我们在基因敲除小鼠中进行了一系列行为测试。在行为实验中，基因敲除小鼠具有多种精神分裂症样缺陷，如活动减退和社会交往减少。结果暗示GABA能和大麻素相关功能障碍是精神分裂症分子机制的关键组成部分。

Studies have provided evidence for abnormalities of the GABAergic system in schizophrenia. Cannabinoid receptors may play a role in modulating GABAergic neurons. In this study, we have performed the genetic analysis of the GABAergic neural transmission and the cannabinoid pathway in the pathophysiology of schizophrenia.We examined the association of genetic variation with the disease and the alteration of gene expression in post-mortem schizophrenic brain. We found the evidence that a number of the genes in these signaling pathways are related to the disease. In addition, we conducted a series of behavioral tests in knockout mice. In behavioral experiments, knockout mice of the genes have multiple schizophrenia-like defects such as hypoactivity and reduced social interaction.The results implicate GABAergic and cannabinoid-related dysfunctions as a key component of the molecular mechanism of schizophrenia.