Gene Exression in the Substantina Nigra of Subjects with Schizophrenia

我们测试了我们的假设，即GABA神经传递的投射神经元在黑质网状部（SNR）的减少和多巴胺神经元在黑质网状部（SNC）是过度活跃的结果。我们分析了GAD 67，GABA合成酶，酪氨酸羟化酶（TH），多巴胺合成酶，和KCNS 3电压门控钾通道亚基在SNR和SNC的14对控制和性别和年龄匹配的精神分裂症患者的基因表达，使用原位杂交。在SNR中，GAD 67 mRNA水平在对照组和精神分裂症受试者之间没有差异。与此相反，TH和KCNS3 mRNA水平显着较低的SNC精神分裂症患者。我们的结果不支持SNR神经元改变GABA神经传递。然而，KCNS3表达减少可增强SNC多巴胺神经元的兴奋性，有助于阳性症状。低TH水平可能反映了一种补偿机制。

We tested our hypothesis that GABA neurotransmission by projection neurons in the substantia nigra pars reticulata (SNR) is reduced and dopamine neurons in the substantia nigra pars compacta (SNC) are hyperactive as the result. We analyzed gene expression for GAD67, an enzyme for GABA synthesis, tyrosine hydroxylase (TH), an enzyme for dopamine synthesis, and KCNS3 voltage-gated potassium channel subunit in the SNR and SNC of 14 pairs of control and sex- and age-matched schizophrenia subjects, using in situ hybridization. In the SNR, GAD67 mRNA levels did not differ between control and schizophrenia subjects. In contrast, TH and KCNS3 mRNA levels were significantly lower in the SNC of schizophrenia subjects. Our results did not support altered GABA neurotransmission by SNR neurons. However, decreased KCNS3 expression could enhance excitability of SNC dopamine neurons, contributing to positive symptoms. Lower TH levels might reflect a compensatory mechanism.