PI3K/AKT pathway mediates the antidepressant- and anxiolytic-like roles of hydrogen sulfide in streptozotocin-induced diabetic rats via promoting hippocampal neurogenesis |
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| Affiliation: | 1. Department of Neurology, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, PR China;2. Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China;3. Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, PR China;1. Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China;2. Department of Emergency, The Second Affiliated Hospital and Yuying Children''s Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China;3. Institute of Life Sciences, Wenzhou University, Wenzhou 325035, Zhejiang, China;4. Department of Neurosurgery, Cixi People''s Hospital, Wenzhou Medical University, Ningbo 315300, Zhejiang, China;5. Science and Education Division, Cixi People''s Hospital, Wenzhou Medical University, Ningbo 315300, Zhejiang, China;6. Experimental Research Centre, Dongyang People''s Hospital, Wenzhou Medical University, Jinhua 322100, Zhejiang, China;1. Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi;2. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan |
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| Abstract: | 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 STZ-induced 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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| Keywords: | Diabetes Depression Hydrogen sulfide PI3K/AKT pathway Hippocampal neurogenesis |
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