Low corticosterone levels attenuate late life depression and enhance glutamatergic neurotransmission in female rats

被引：13

作者：

Chu, Shi-feng ^{[1
,2
]}

Zhang, Zhao ^{[1
,2
]}

Zhou, Xin ^{[1
,2
]}

He, Wen-bin ^{[3
]}

Yang, Bo ^{[4
]}

Cui, Li-yuan ^{[1
,2
]}

He, Hong-yuan ^{[5
]}

Wang, Zhen-zhen ^{[1
,2
]}

Chen, Nai-hong ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing 100050, Peoples R China

[3] Shanxi Univ Chinese Med, Shanxi Key Lab Chinese Med Encephalopathy, Jinzhong 030619, Peoples R China

[4] Characterist Med Ctr Chinese Peoples Armed Police, Dept Pharm, Tianjin 300300, Peoples R China

[5] Tianjin Univ Tradit Chinese Med, Tianjin 301617, Peoples R China

来源：

ACTA PHARMACOLOGICA SINICA | 2021年 / 42卷 / 06期

基金：

中国国家自然科学基金;

关键词：

major depression disorder; late life depression; corticosterone; hippocampus; glutamatergic transmission; glutamate; glutamine cycle; glutamate transporter 1; LONG-TERM POTENTIATION; PREFRONTAL CORTEX; COLLABORATIVE CARE; STRESS; BRAIN; GLUCOCORTICOIDS; EXPRESSION; HIPPOCAMPUS; MECHANISMS; SYNAPTOSOMES;

D O I：

10.1038/s41401-020-00536-w

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Sustained elevation of corticosterone (CORT) is one of the common causes of aging and major depression disorder. However, the role of elevated CORT in late life depression (LLD) has not been elucidated. In this study, 18-month-old female rats were subjected to bilateral adrenalectomy or sham surgery. Their CORT levels in plasma were adjusted by CORT replacement and the rats were divided into high-level CORT (H-CORT), low-level CORT (L-CORT), and Sham group. We showed that L-CORT rats displayed attenuated depressive symptoms and memory defects in behavioral tests as compared with Sham or H-CORT rats. Furthermore, we showed that glutamatergic transmission was enhanced in L-CORT rats, evidenced by enhanced population spike amplitude (PSA) recorded from the dentate gyrus of hippocampus in vivo and increased glutamate release from hippocampal synaptosomes caused by high frequency stimulation or CORT exposure. Intracerebroventricular injection of an enzymatic glutamate scavenger system, glutamic-pyruvic transmine (GPT, 1 mu M), significantly increased the PSA in Sham rats, suggesting that extracelluar accumulation of glutamate might be the culprit of impaired glutamatergic transmission, which was dependent on the uptake by Glt-1 in astrocytes. We revealed that hippocampal Glt-1 expression level in the L-CORT rats was much higher than in Sham and H-CORT rats. In a gradient neuron-astrocyte coculture, we found that the expression of Glt-1 was decreased with the increase of neural percentage, suggesting that impairment of Glt-1 might result from the high level of CORT contributed neural damage. In sham rats, administration of DHK that inhibited Glt-1 activity induced significant LLD symptoms, whereas administration of RIL that promoted glutamate uptake significantly attenuated LLD. All of these results suggest that glutamatergic transmission impairment is one of important pathogenesis in LLD induced by high level of CORT, which provide promising clues for the treatment of LLD.

引用

页码：848 / 860

页数：13

共 62 条

[1] Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory [J].