Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuou-ku, Chiba, Chiba, 260-8670, Japan.
Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuou-ku, Chiba, Chiba, 260-8670, Japan.
Behav Brain Res. 2021 Mar 5;401:113092. doi: 10.1016/j.bbr.2020.113092. Epub 2020 Dec 28.
Clinical studies have demonstrated that allopregnanolone (3α5α-tetrahydroprogesterone, ALLO) has antidepressant-like effects on patients with depression. Previous studies have shown alteration of the astroglial glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) in depression, and ALLO is known to modulate glutamate release. The present study aimed to investigate whether astroglial GLT-1 and GS are indeed involved in the antidepressant-like effects of ALLO in learned helplessness (LH) rats, a validated animal model of depression. The results of this study showed that bilateral microinjection of ALLO into the lateral ventricles could normalize the levels of GLT-1 and GS in the nucleus accumbens (NAc) and of GS in the hippocampal CA1 region of LH rats. These results suggest a certain connection between the antidepressant-like effects of ALLO and the astroglial GLT-1/GS system of the NAc in LH rats.
临床研究表明，别孕烯醇酮（3α5α-四氢孕酮，ALLO）对抑郁症患者具有抗抑郁作用。先前的研究表明，抑郁症患者的星形胶质细胞谷氨酸转运体-1（GLT-1）和谷氨酰胺合成酶（GS）发生改变，而 ALLO 已知可调节谷氨酸释放。本研究旨在探讨星形胶质细胞 GLT-1 和 GS 是否确实参与了别孕烯醇酮在习得性无助（LH）大鼠中的抗抑郁作用，LH 大鼠是一种经过验证的抑郁症动物模型。该研究结果表明，将 ALLO 双侧微注射到侧脑室可使 LH 大鼠伏隔核（NAc）中的 GLT-1 和 GS 以及海马 CA1 区中的 GS 水平正常化。这些结果表明，ALLO 的抗抑郁作用与 LH 大鼠 NAc 中的星形胶质细胞 GLT-1/GS 系统之间存在一定联系。
