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The alterations of glutamate transporter 1 and glutamine synthetase in the rat brain of a learned helplessness model of depression.
Psychopharmacology ( IF 3.4 ) Pub Date : 2020-05-22 , DOI: 10.1007/s00213-020-05555-3
Kouhei Yoshino 1 , Yasunori Oda 1 , Makoto Kimura 1 , Hiroshi Kimura 1 , Masahito Nangaku 1 , Yukihiko Shirayama 2 , Masaomi Iyo 1
Affiliation  

Background

Although glutamate transmission via astrocytes has been proposed to contribute to the pathophysiology of depression, the precise mechanisms are unknown. Herein, we investigated the levels of glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) of astrocytes in learned helplessness (LH) rats (an animal model of depression) and non-LH rats (an animal model of resilience).

Methods

We administered inescapable mild electric shock to rats and then discriminated the LH and non-LH rats by a post-shock test. Almost 55% of the rats acquired LH. We then measured the expressions of GLT-1 and GS in several brain regions of LH and non-LH rats by Western blot analysis.

Results

The levels of GLT-1 and GS in the CA-1, CA-3, dentate gyrus (DG), medial prefrontal cortex (mPF), and nucleus accumbens (NAc) of the LH group were significantly higher than those of the control group. The GS levels in the amygdala of the LH rats were significantly decreased compared to the controls. There were significant differences in GLT-1 and GS levels between the non-LH and LH rats in the CA-1 and CA-3.

Conclusions

These results suggest that the LH rats experienced up-regulations of GLT-1 and GS in the CA-1, CA-3, DG, mPF, and NAc and a down-regulation of GS in the amygdala. It is possible that the effects of the GLT-1 and GS levels on astrocytes in the CA-1 and CA-3 are critical for the differentiation of resilience from vulnerability.



中文翻译:

学习型抑郁无助模型的大鼠脑中谷氨酸转运蛋白1和谷氨酰胺合成酶的变化。

背景

尽管已提出通过星形胶质细胞传递谷氨酸有助于抑郁症的病理生理,但确切的机制尚不清楚。在这里,我们调查了学习无助(LH)大鼠(抑郁症的动物模型)和非LH大鼠(弹性动物模型)的星形胶质细胞谷氨酸转运蛋白-1(GLT-1)和谷氨酰胺合成酶(GS)的水平。

方法

我们对大鼠进行了不可避免的轻度电击,然后通过电击后测试区分了LH和非LH大鼠。几乎55%的大鼠获得了LH。然后,我们通过Western印迹分析测量了LH和非LH大鼠几个大脑区域中GLT-1和GS的表达。

结果

LH组的CA-1,CA-3,齿状回(DG),内侧前额叶皮层(mPF)和伏隔核(NAc)中GLT-1和GS的水平显着高于对照组。与对照组相比,LH大鼠杏仁核中的GS水平显着降低。在CA-1和CA-3中,非LH和LH大鼠之间的GLT-1和GS水平存在显着差异。

结论

这些结果表明,LH大鼠在CA-1,CA-3,DG,mPF和NAc中经历了GLT-1和GS的上调,在杏仁核中经历了GS的下调。GLT-1和GS水平对CA-1和CA-3中星形胶质细胞的影响可能对于区分韧性和脆弱性至关重要。

更新日期:2020-07-10
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