Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases.
Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases.
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DOI：
10.1016/j.neuroscience.2012.01.033
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发表时间：
2012-04-05
期刊：
影响因子：
3.3
通讯作者：
Stevens, K. E.
中科院分区：
文献类型：
--
作者：
Adams, C. E.;Yonchek, J. C.;Schulz, K. M.;Graw, S. L.;Stitzel, J.;Teschke, P. U.;Stevens, K. E.
CHRNA7（人）/Chrna7（小鼠）编码的 α7* 烟碱乙酰胆碱受体调节海马结构中抑制性神经递质 γ-氨基丁酸 (GABA) 和兴奋性神经递质谷氨酸的释放。 15q13.3 含有 CHRNA7 的杂合缺失与精神分裂症、自闭症和癫痫的风险增加相关。这些疾病中的每一种都以兴奋性和抑制性海马回路功能异常为特征。在 Chrna7 无效突变杂合的 C3H 小鼠中，Chrna7 表达减少会导致海马 α7* 受体密度降低、海马听觉感觉处理异常以及海马 CA3 锥体神经元活性增加。这些异常表明 Chrna7 表达减少会改变海马抑制回路功能。目前的研究通过测量野生型 (Chrna7 +/+) 和杂合型 (Chrna7 +/-) C3H 中 GABA、GABAA 受体、GABA 合成酶谷氨酸脱羧酶-65 (GAD-65) 和囊泡 GABA 转运蛋白 GAT-1 的水平，研究了 Chrna7 表达减少对海马抑制回路的具体影响。 两种性别的α7小鼠。雄性和雌性杂合子 C3H α7 小鼠中的 GAD-65 水平显着降低，而 GABAA 受体仅在雄性杂合子 C3H α7 小鼠中显着降低。未检测到 GABA 和 GAT-1 水平的变化。这些数据表明，CHRNA7 表达减少可能导致精神分裂症、自闭症和/或癫痫症中观察到的海马抑制回路异常。
The α7* nicotinic acetylcholine receptor encoded by CHRNA7 (human)/Chrna7 (mice) regulates the release of both the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the excitatory neurotransmitter glutamate in the hippocampal formation. A heterozygous deletion at 15q13.3 containing CHRNA7 is associated with increased risk for schizophrenia, autism and epilepsy. Each of these diseases is characterized by abnormalities in excitatory and inhibitory hippocampal circuit function. Reduced Chrna7 expression results in decreased hippocampal α7* receptor density, abnormal hippocampal auditory sensory processing and increased hippocampal CA3 pyramidal neuron activity in C3H mice heterozygous for a null mutation in Chrna7. These abnormalities demonstrate that decreased Chrna7 expression alters hippocampal inhibitory circuit function. The current study examined the specific impact of reduced Chrna7 expression on hippocampal inhibitory circuits by measuring the levels of GABA, GABAA receptors, the GABA synthetic enzyme glutamate decarboxylase-65 (GAD-65) and the vesicular GABA transporter GAT-1 in wild type (Chrna7 +/+) and heterozygous (Chrna7 +/−) C3H α7 mice of both genders. GAD-65 levels were significantly decreased in male and female heterozygous C3H α7 mice while GABAA receptors were significantly reduced only in male heterozygous C3H α7 mice. No changes in GABA and GAT-1 levels were detected. These data suggest that reduced CHRNA7 expression may contribute to the abnormalities in hippocampal inhibitory circuits observed in schizophrenia, autism and/or epilepsy.
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影响因子：
30.8
作者：
Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
7.6
作者：
Glausier, Jill R.;Lewis, David A.
通讯作者：
Lewis, David A.
影响因子：
5.3
作者：
Bitner, Robert S.;Bunnelle, William H.;Gopalakrishnan, Murali
通讯作者：
Gopalakrishnan, Murali
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW
DOI：
10.1007/7854_2010_43
发表时间：
2010-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF SCHIZOPHRENIA AND ITS TREATMENT
影响因子：
--
作者：
Heckers, Stephan;Konradi, Christine
通讯作者：
Konradi, Christine