The function and mechanism of GABAergic signaling in schizophrenia

研究为精神分裂症患者GABA能系统的异常提供了证据。大麻素受体可能在GABA能神经元的调节中发挥作用。在这项研究中，我们对精神分裂症病理生理学中的GABA能神经传递和大麻素途径进行了遗传分析，并研究了遗传变异与疾病的关系以及死后精神分裂症脑中基因表达的变化。我们发现有证据表明，这些信号通路中的一些基因与这种疾病有关。此外，我们还在基因敲除小鼠身上进行了一系列行为测试。在行为学实验中，该基因敲除的小鼠具有多种精神分裂症样缺陷，如活动不足和社交互动减少。结果表明，GABA能和大麻素相关的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.