Defects in dendrite and spine maturation and synaptogenesis associated with an anxious-depressive-like phenotype of GABAA receptor-deficient mice.
Defects in dendrite and spine maturation and synaptogenesis associated with an anxious-depressive-like phenotype of GABAA receptor-deficient mice.
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DOI：
10.1016/j.neuropharm.2014.07.019
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发表时间：
2015-01
影响因子：
4.7
通讯作者：
Luscher B
中科院分区：
文献类型：
--
作者：
Ren Z;Sahir N;Murakami S;Luellen BA;Earnheart JC;Lal R;Kim JY;Song H;Luscher B
GABAA受体γ2亚基杂合小鼠（γ2+/−小鼠）已被广泛表征为重度抑郁症的模型。这些小鼠的表型包括表现为焦虑、绝望和快感缺乏的行为，以及海马依赖性模式分离、HPA轴活动过度和抗抑郁药物反应性增加的缺陷。因此，γ2+/−模型为重性抑郁症的GABA能缺陷假说提供了强有力的支持。在这里，我们发现γ2+/−小鼠在成年海马颗粒细胞的晚期存活中还表现出特定的缺陷，包括树突状细胞复杂性降低和突触棘成熟受损。此外，体外培养的皮质γ2+/−神经元在模拟成年海马颗粒细胞环境的竞争性条件下生长时，选择性地表现出明显的GABA能神经支配缺陷。最后，γ2+/−小鼠的脑提取物显示出三周龄时脑源性神经营养因子（BDNF）表达短暂减少的数值但不显著的趋势（p = 0.06），这可能有助于先前报道的γ2+/−小鼠行为表型的发育起源。这些数据表明，重性抑郁症的GABA能、谷氨酸能、基于压力和神经营养缺陷假说越来越一致。
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.
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影响因子：
5.3
作者：
Earnheart, John C.;Schweizer, Claude;Luscher, Bernhard
通讯作者：
Luscher, Bernhard
影响因子：
25
作者：
Essrich, C;Lorez, M;Lüscher, B
通讯作者：
Lüscher, B
DOI：
10.1523/jneurosci.4991-10.2011
发表时间：
2011-02-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen AI;Nguyen CN;Copenhagen DR;Badurek S;Minichiello L;Ranscht B;Reichardt LF
通讯作者：
Reichardt LF
影响因子：
6.9
作者：
Austin, MP;Mitchell, P;Hadzi-Pavlovic, D
通讯作者：
Hadzi-Pavlovic, D
影响因子：
5.3
作者：
Ashby, Michael C.;Maier, Susie R.;Henley, Jeremy M.
通讯作者：
Henley, Jeremy M.