加巴能
神经科学
海马结构
γ-氨基丁酸受体
谷氨酸的
神经营养因子
神经营养素
突触发生
生物
齿状回
表型
内分泌学
心理学
内科学
受体
抑制性突触后电位
医学
谷氨酸受体
遗传学
基因
作者
Zhen Ren,Nadia Sahir,Shoko Murakami,Beth A. Luellen,John C. Earnheart,Rachnanjali Lal,Ju Young Kim,Hongjun Song,Bernhard Lüscher
标识
DOI:10.1016/j.neuropharm.2014.07.019
摘要
Mice that were rendered heterozygous for the γ2 subunit of GABAA receptors (γ2+/− mice) have been characterized extensively as a model for major depressive disorder. The phenotype of these mice includes behavior indicative of heightened anxiety, despair, and anhedonia, as well as defects in hippocampus-dependent pattern separation, HPA axis hyperactivity and increased responsiveness to antidepressant drugs. The γ2+/− model thereby provides strong support for the GABAergic deficit hypothesis of major depressive disorder. Here we show that γ2+/− mice additionally exhibit specific defects in late stage survival of adult-born hippocampal granule cells, including reduced complexity of dendritic arbors and impaired maturation of synaptic spines. Moreover, cortical γ2+/− neurons cultured in vitro show marked deficits in GABAergic innervation selectively when grown under competitive conditions that may mimic the environment of adult-born hippocampal granule cells. Finally, brain extracts of γ2+/− mice show a numerical but insignificant trend (p = 0.06) for transiently reduced expression of brain derived neurotrophic factor (BDNF) at three weeks of age, which might contribute to the previously reported developmental origin of the behavioral phenotype of γ2+/− mice. The data indicate increasing congruence of the GABAergic, glutamatergic, stress-based and neurotrophic deficit hypotheses of major depressive disorder. This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’.
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