Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron-astrocyte-microglia dysregulation.
Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron-astrocyte-microglia dysregulation.
复制标题
Gabrb2 基因敲除小鼠表现出精神分裂症样和合并症表型，伴有中间神经元-星形胶质细胞-小胶质细胞失调。
DOI：
10.1038/s41398-018-0176-9
复制
发表时间：
2018-07-17
影响因子：
6.8
通讯作者：
Xue H
中科院分区：
文献类型：
--
作者：
Yeung RK;Xiang ZH;Tsang SY;Li R;Ho TYC;Li Q;Hui CK;Sham PC;Qiao MQ;Xue H
Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure. In addition, the KO mice were highly susceptible to audiogenic epilepsy. Some of the behavioral phenotypes showed evidence of imprinting, gender effect and amelioration by the antipsychotic risperidone, and the audiogenic epilepsy was inhibited by the antiepileptic diazepam. GABAergic parvalbumin (PV)-positive interneuron dystrophy, astrocyte dystrophy, and extensive microglia activation were observed in the frontotemporal corticolimbic regions, and reduction of newborn neurons was observed in the hippocampus by immunohistochemical staining. The neuroinflammation indicated by microglial activation was accompanied by elevated brain levels of oxidative stress marker malondialdehyde (MDA) and the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These extensive schizophrenia-like and comorbid phenotypes brought about by Gabrb2 knockout, in conjunction with our previous findings on GABRB2 association with schizophrenia, support a pivotal role of GABRB2 in schizophrenia etiology.
登录
查看更多内容
影响因子：
4.5
作者：
Heckers, Stephan;Konradi, Christine
通讯作者：
Konradi, Christine
影响因子：
3.3
作者：
Hörtnagl H;Tasan RO;Wieselthaler A;Kirchmair E;Sieghart W;Sperk G
通讯作者：
Sperk G
影响因子：
6.9
作者：
Emiliani FE;Sedlak TW;Sawa A
通讯作者：
Sawa A
影响因子：
3.7
作者：
Cerbai F;Lana D;Nosi D;Petkova-Kirova P;Zecchi S;Brothers HM;Wenk GL;Giovannini MG
通讯作者：
Giovannini MG
影响因子：
3.9
作者：
Chen, Jianhuan;Tsang, Shui-Ying;Xue, Hong
通讯作者：
Xue, Hong