Expression of GABAA α2-, β1- and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder.
Expression of GABAA α2-, β1- and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder.
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DOI：
10.1038/tp.2013.64
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发表时间：
2013-09-10
影响因子：
6.8
通讯作者：
Thuras PD
中科院分区：
文献类型：
--
作者：
Fatemi SH;Folsom TD;Rooney RJ;Thuras PD
大量证据表明，γ-氨基丁酸能信号系统功能障碍参与了精神分裂症和心境障碍的病理过程。关于精神分裂症和情绪障碍患者大脑中GABA受体亚单位蛋白表达的变化，人们知之甚少。我们先前已经证明GABAB受体亚基1和2(GABBR1和GABBR2)在精神分裂症、双相情感障碍和严重抑郁障碍受试者的外侧小脑中表达减少。在本研究中，我们扩大了这些研究的范围，以检测来自同一组精神分裂症(N=9-15)、双相情感障碍(N=10-15)和重度抑郁症(N=12-15)与健康对照组(N=10-15)的外侧小脑中12个GABAA亚单位蛋白(α1、α2、α3、α5、α6、β1、β2、β3、δ，ɛ，γ2和γ3)的基因和蛋白表达。我们发现，在不同的治疗组中，α2-、β1-和ɛ-亚基的蛋白水平存在显著的群体效应。我们还发现，在不同的治疗组之间，α1亚单位的mR NA水平存在显著的群体效应。新的治疗途径，如使用神经类固醇来促进GABA调节，可能会改善这些疾病的GABA能功能障碍。
There is abundant evidence that dysfunction of the γ-aminobutyric acid (GABA)ergic signaling system is implicated in the pathology of schizophrenia and mood disorders. Less is known about the alterations in protein expression of GABA receptor subunits in brains of subjects with schizophrenia and mood disorders. We have previously demonstrated reduced expression of GABAB receptor subunits 1 and 2 (GABBR1 and GABBR2) in the lateral cerebella of subjects with schizophrenia, bipolar disorder and major depressive disorder. In the current study, we have expanded these studies to examine the mRNA and protein expression of 12 GABAA subunit proteins (α1, α2, α3, α5, α6, β1, β2, β3, δ, ɛ, γ2 and γ3) in the lateral cerebella from the same set of subjects with schizophrenia (N=9–15), bipolar disorder (N=10–15) and major depression (N=12–15) versus healthy controls (N=10–15). We found significant group effects for protein levels of the α2-, β1- and ɛ-subunits across treatment groups. We also found a significant group effect for mRNA levels of the α1-subunit across treatment groups. New avenues for treatment, such as the use of neurosteroids to promote GABA modulation, could potentially ameliorate GABAergic dysfunction in these disorders.
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影响因子：
4.7
作者：
Charych, Erik I.;Liu, Feng;Moss, Stephen J.;Brandon, Nicholas J.
通讯作者：
Brandon, Nicholas J.
影响因子：
10.6
作者：
Enoch, Mary-Anne;Hodgkinson, Colin A.;Yuan, Qiaoping;Shen, Pei-Hong;Goldman, David;Roy, Alec
通讯作者：
Roy, Alec
DOI：
10.1073/pnas.93.18.9985
发表时间：
1996-09-03
影响因子：
11.1
作者：
Andreasen, NC;OLeary, DS;Hichwa, RD
通讯作者：
Hichwa, RD
影响因子：
--
作者：
Baldaçara, Leonardo;Borgio, João Guilherme Fiorani;Jackowski, Andrea Parolin
通讯作者：
Jackowski, Andrea Parolin
影响因子：
3.9
作者：
Chen, Jianhuan;Tsang, Shui-Ying;Xue, Hong
通讯作者：
Xue, Hong