Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.
Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.
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精神分裂症前额叶皮层中含白蛋白的神经元中KCNS3钾通道亚基的基因表达较低。
DOI：
10.1176/appi.ajp.2013.13040468
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Hashimoto T
中科院分区：
文献类型：
--
作者：
Georgiev D;Arion D;Enwright JF;Kikuchi M;Minabe Y;Corradi JP;Lewis DA;Hashimoto T
在精神分裂症中，皮质GABA神经传递标志物的改变在含小清蛋白的神经元中是突出的。小清蛋白神经元选择性表达KCNS3，KCNS3是编码Kv9.3钾通道α亚基的基因。Kv9.3亚基存在于电压门控钾通道中，其有助于精确检测对小清蛋白神经元的一致兴奋性突触输入。小白蛋白神经元的这种独特特征对于γ振荡中皮层神经网络的同步化显得很重要。由于受损的前额叶皮层γ振荡被认为是精神分裂症认知障碍的基础，作者研究了精神分裂症受试者前额叶皮层中KCNS 3 mRNA水平是否发生改变。KCNS3 mRNA的表达进行了评估，通过原位杂交在22对匹配的精神分裂症和对照组，并通过微阵列分析的合并样本的单独解剖的神经元标记与野豌豆凝集素（VVA），小白蛋白神经元选择性标记，在一个单独的队列的14对。慢性抗精神病药物治疗对KCNS3表达的影响在抗精神病药物暴露的猴子的前额叶皮层中进行了测试。通过原位杂交，KCNS3 mRNA水平在精神分裂症患者中降低了23%。在细胞水平上，表达KCNS 3 mRNA的神经元密度和每个神经元的KCNS 3 mRNA水平均显著降低。通过微阵列，KCNS 3 mRNA水平在精神分裂症患者VVA标记的神经元中降低了40%。KCNS3 mRNA水平在抗精神病药物暴露的猴子中没有改变。这些发现揭示了精神分裂症患者前额叶皮质小清蛋白神经元中KCNS 3表达降低，为小清蛋白神经元的一致突触输入检测受损提供了分子基础，这些突触输入可能导致精神分裂症患者γ振荡改变和认知受损。
In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects. KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys. By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys. These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.
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被诊断为精神分裂症的受试者的杏仁核和内嗅皮层的细胞外基质异常。
影响因子：
--
作者：
Pantazopoulos, Harry;Woo, Tsung-Ung W.;Lim, Maribel P.;Lange, Nicholas;Berretta, Sabina
通讯作者：
Berretta, Sabina
精神分裂症的皮质性白蛋白中间神经元和认知功能障碍。
影响因子：
15.9
作者：
Lewis DA;Curley AA;Glausier JR;Volk DW
通讯作者：
Volk DW
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
DOI：
10.1073/pnas.0500468102
发表时间：
2005-04-26
影响因子：
11.1
作者：
Kerschensteiner, D;Soto, F;Stocker, M
通讯作者：
Stocker, M