Reduced CHRNA7 expression in C3H mice is associated with increases in hippocampal parvalbumin and glutamate decarboxylase-67 (GAD67) as well as altered levels of GABA(A) receptor subunits.
Reduced CHRNA7 expression in C3H mice is associated with increases in hippocampal parvalbumin and glutamate decarboxylase-67 (GAD67) as well as altered levels of GABA(A) receptor subunits.
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DOI：
10.1016/j.neuroscience.2014.05.004
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发表时间：
2014-07-25
期刊：
影响因子：
3.3
通讯作者：
Adams, C. E.
中科院分区：
文献类型：
--
作者：
Bates, R. C.;Stith, B. J.;Stevens, K. E.;Adams, C. E.
关键词：
编码烟碱受体α7*亚型的基因CHRNA7的表达减少，可能通过破坏海马的抑制性/兴奋性平衡而导致精神分裂症患者的认知功能障碍。Chrna7表达降低的C3H小鼠海马α7*受体密度显著降低，海马听觉门控缺陷，海马活动增加，海马谷氨酸脱羧酶-65 （GAD65）和γ-氨基丁酸-a （GABAA）受体水平显著降低。本研究利用定量western免疫印迹技术研究了雄性和雌性C3H Chrna7野生型、C3H Chrna7杂合型和C3H Chrna7敲除型小鼠海马小白蛋白、GAD67和/或GABAA受体亚基水平的变化是否与Chrna7表达改变有关。Chrna7表达的减少与海马小白蛋白和GAD67的显著增加以及GABAA受体亚基的复杂改变有关。雌性C3H Chrna7 Het和KO小鼠α3亚基蛋白表达均降低，而雌性C3H Chrna7 KO小鼠α4亚基蛋白表达均降低，无性别差异。相比之下，在C3H Chrna7 Het小鼠中观察到δ亚基蛋白的增加，而在C3H Chrna7 KO小鼠中观察到该亚基蛋白的减少，并且雄性的δ亚基蛋白水平高于雌性。最后，在C3H Chrna7 KO小鼠中发现γ - 2亚基蛋白增加，且该亚基在雄性小鼠中的水平也高于雌性小鼠。在C3H Chrna7小鼠中观察到的海马小白蛋白和GAD67的增加与报告中精神分裂症患者死后海马中这些蛋白的减少相反。我们假设不同的结果可能是由于在精神分裂症中发现异常的CHRNA7以外的其他因素的影响。
Decreased expression of CHRNA7, the gene encoding the α7* subtype of nicotinic receptor, may contribute to the cognitive dysfunction observed in schizophrenia by disrupting the inhibitory/excitatory balance in the hippocampus. C3H mice with reduced Chrna7 expression have significant reductions in hippocampal α7* receptor density, deficits in hippocampal auditory gating, increased hippocampal activity as well as significant decreases in hippocampal glutamate decarboxylase-65 (GAD65) and γ-aminobutyric acid-A (GABAA) receptor levels. The current study investigated whether altered Chrna7 expression is associated with changes in the levels of parvalbumin, GAD67 and/or GABAA receptor subunits in hippocampus from male and female C3H Chrna7 wildtype, C3H Chrna7 heterozygous and C3H Chrna7 knockout mice using quantitative western immunoblotting. Reduced Chrna7 expression was associated with significant increases in hippocampal parvalbumin and GAD67 and with complex alterations in GABAA receptor subunits. A decrease in α3 subunit protein was seen in both female C3H Chrna7 Het and KO mice while a decrease in α4 subunit protein was also detected in C3H Chrna7 KO mice with no sex difference. In contrast, an increase in δ subunit protein was observed in C3H Chrna7 Het mice while a decrease in this subunit was observed in C3H Chrna7 KO mice, with δ subunit protein levels being greater in males than in females. Finally, an increase in γ2 subunit protein was found in C3H Chrna7 KO mice with the levels of this subunit again being greater in males than in females. The increases in hippocampal parvalbumin and GAD67 observed in C3H Chrna7 mice are contrary to reports of reductions in these proteins in postmortem hippocampus from schizophrenic individuals. We hypothesize that the disparate results may occur because of the influence of factors other than CHRNA7 that have been found to be abnormal in schizophrenia.
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影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
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：
3.5
作者：
Dibbens, Leanne M.;Mullen, Saul;Berkovic, Samuel F.
通讯作者：
Berkovic, Samuel F.
影响因子：
3.8
作者：
Arevalo-Serrano, J.;Sanz-Anquela, J. M.;Gonzalo-Ruiz, A.
通讯作者：
Gonzalo-Ruiz, A.
影响因子：
5.3
作者：
Hashimoto, T;Bergen, SE;Lewis, DA
通讯作者：
Lewis, DA