Department of Internal Medicine, Rambam Medical Center, B Rappaport Faculty of Medicine and B Rappaport Research Institute, Technion, Haifa Israel.
Int J Neuropsychopharmacol. 2012 Aug;15(7):869-82. doi: 10.1017/S1461145711001428. Epub 2011 Oct 19.
Evidence concerning ion-channel abnormalities in the pathophysiology of common psychiatric disorders is still limited. Given the significance of ion channels in neuronal activity, neurotransmission and neuronal plasticity we hypothesized that the expression patterns of genes encoding different ion channels may be altered in schizophrenia, bipolar and unipolar disorders. Frozen samples of striatum including the nucleus accumbens (Str-NAc) and the lateral cerebellar hemisphere of 60 brains from depressed (MDD), bipolar (BD), schizophrenic and normal subjects, obtained from the Stanley Foundation Brain Collection, were assayed. mRNA of 72 different ion-channel subunits were determined by qRT-PCR and alteration in four genes were verified by immunoblotting. In the Str-NAc the prominent change was observed in the MDD group, in which there was a significant up-regulation in genes encoding voltage-gated potassium-channel subunits. However, in the lateral cerebellar hemisphere (cerebellum), the main change was observed in schizophrenia specimens, as multiple genes encoding various ion-channel subunits were significantly down-regulated. The impaired expression of genes encoding ion channels demonstrates a disease-related neuroanatomical pattern. The alterations observed in Str-NAc of MDD may imply electrical hypo-activity of this region that could be of relevance to MDD symptoms and treatment. The robust unidirectional alteration of both excitatory and inhibitory ion channels in the cerebellum may suggests cerebellar general hypo-transcriptional activity in schizophrenia.
关于常见精神疾病病理生理学中离子通道异常的证据仍然有限。鉴于离子通道在神经元活动、神经递质传递和神经元可塑性中的重要性，我们假设编码不同离子通道的基因的表达模式可能在精神分裂症、双相和单相障碍中发生改变。从 Stanley 基金会脑库获得了 60 个来自抑郁（MDD）、双相（BD）、精神分裂症和正常受试者的冷冻的纹状体（包括伏隔核（Str-NAc）和外侧小脑半球）样本，通过 qRT-PCR 测定了 72 种不同离子通道亚基的 mRNA，并通过免疫印迹验证了四个基因的变化。在 Str-NAc 中，MDD 组观察到明显变化，其中编码电压门控钾通道亚基的基因显著上调。然而，在外侧小脑半球（小脑）中，主要变化发生在精神分裂症标本中，因为多种编码各种离子通道亚基的基因显著下调。离子通道编码基因的表达受损表明存在与疾病相关的神经解剖模式。MDD 中 Str-NAc 观察到的改变可能意味着该区域的电活动不足，这可能与 MDD 症状和治疗有关。小脑中兴奋性和抑制性离子通道的一致单向改变可能表明精神分裂症小脑总体转录活性降低。
