1. Academic Validation
  2. Harmine produces antidepressant-like effects via restoration of astrocytic functions

Harmine produces antidepressant-like effects via restoration of astrocytic functions

  • Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):258-267. doi: 10.1016/j.pnpbp.2017.06.012.
Fengguo Liu 1 Jingjing Wu 2 Yu Gong 3 Peng Wang 3 Lei Zhu 4 Lijuan Tong 3 Xiangfan Chen 3 Yong Ling 3 Chao Huang 5
Affiliations

Affiliations

  • 1 Department of Neurology, Danyang People's Hospital, #2 Xinmin Western Road, Danyang 212300, Jiangsu, China.
  • 2 Department of Cardiology, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, #118 Wansheng Street, Suzhou 215021, Jiangsu, China.
  • 3 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu, China; Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, #19 Qixiu Road, Nantong 226001, Jiangsu, China.
  • 4 Department of Pharmacy, First People's Hospital of Yancheng, Yulong Western Road, Yancheng 224006, Jiangsu, China.
  • 5 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu, China; Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, #19 Qixiu Road, Nantong 226001, Jiangsu, China. Electronic address: huachao@ntu.edu.cn.
Abstract

Depression is a world-wide disease with no effective therapeutic methods. Increasing evidence indicates that astrocytic pathology contributes to the formation of depression. In this study, we investigated the effects of harmine, a natural β-carboline alkaloid and potent hallucinogen, known to modulate astrocytic glutamate transporters, on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. Results showed that harmine treatment (10, 20mg/kg) protected the mice against the CUS-induced increases in the immobile time in the tail suspension test (TST) and forced swimming test (FST), and also reversed the reduction in sucrose intake in the sucrose preference experiment. Harmine treatment (20mg/kg) prevented the reductions in brain-derived neurotrophic factor (BDNF) protein levels and hippocampal neurogenesis induced by CUS. In addition, harmine treatment (20mg/kg) increased the protein expression levels of glutamate transporter 1 (GLT-1) and prevented the CUS-induced decreases in glial fibrillary acidic protein (GFAP) protein expressions in the prefrontal cortex and hippocampus, suggesting that restoration of astrocytic functions may be a potential mechanism underlying the antidepressant-like effects of harmine. This opinion was proved by the results that administration of mice with l-Alpha-Aminoadipic Acid (L-AAA), a gliotoxin specific for astrocytes, attenuated the antidepressant-like effects of harmine, and prevented the improvement effects of harmine on BDNF protein levels and hippocampal neurogenesis. These results provide further evidence to confirm that astrocytic dysfunction contributes critically to the development of depression and that harmine exerts antidepressant-like effects likely through restoration of astrocytic functions.

Keywords

Astrocyte; Chronic unpredictable stress; Depression; Glutamate transporter 1; Harmine.

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