期刊
NEUROTOXICOLOGY
卷 85, 期 -, 页码 201-208出版社
ELSEVIER
DOI: 10.1016/j.neuro.2021.05.016
关键词
Diabetes; Depression; Hydrogen sulfide; PI3K; AKT pathway; Hippocampal neurogenesis
资金
- National Natural Science Foundation of China [81971267]
- Natural Science Foundation of Hunan Province [2019JJ50546, 2019JJ80057]
- Hunan Provincial Innovation Foundation for Postgraduate [CX20200980]
The study demonstrates that hydrogen sulfide improves depression- and anxiety-like behaviors in diabetic rats by activating the hippocampal PI3K/AKT pathway and enhancing hippocampal neurogenesis. This finding enhances our understanding of the therapeutic potential of hydrogen sulfide as a treatment strategy for depression in diabetes mellitus.
We have previously demonstrated that hydrogen sulfide (H2S), the third endogenous gasotransmitter, ameliorates the depression- and anxiety-like behaviors in diabetic rats, but the underlying mechanism remains unclear. The present was aimed to investigate whether the hippocampal phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway mediates H2S-ameliorated depression- and anxiety-like behaviors in diabetic rats by improving the hippocampal neurogenesis. The depression-like behaviors were examined by Tail suspension test (TST), the anxiety-like behaviors were examined by Elevated plus maze test (EPM), and the locomotor activity was detected by Open Field Test (OFT). The expressions of doublecortin (DCX), neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), p-AKT, and AKT in the hippocampus were determined by Western blot analysis. Results showed that NaHS, a donor of exogenous H2S, not only activated the hippocampal PI3K/AKT pathway, as evidenced by the increase of phosphorylated AKT, but also favorably reversed streptozotocin (STZ)-disturbed hippocampal neurogenesis, as evidenced by the increases in the expressions of DCX and NeuN as well as the decrease in the expression of GFAP in the hippocampus of STZ-induced diabetic rats. Furthermore, inhibited PI3K/AKT pathway by LY294002 significantly abolished H2S-exerted the improvement of hippocampal neurogenesis and the antidepressant- and anxiolytic-like effects in the STZ-induced diabetic rats. Taken together, these results uncover that the activation of hippocampal PI3K/AKT pathway plays an important role to restore hippocampal neurogenesis and subsequently to mediate the antidepressant- and anxiolytic-like roles of H2S in STZinduced diabetic rats and enhance our understanding of the robustness of H2S as a therapeutic strategy for treatment of depression in diabetes mellitus.
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