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S-Adenosyl Methionine Improves Depression-Like Behaviours and Synaptic Markers by Elevating the Expression of Endogenous Hydrogen Sulfide in the Hippocampus

Author(s): Xuan Luoa, Tong-Yong Fanga, An-lei guoa, Xia Yanga, Yi-peng Panga, Jing Rena, Kelly A. Newellc, Yinghua Yubc, Xu-Feng Huangbc, Yi Liuac


Hydrogen sulfide (H2S) plays an import role in neuroplasticity; deficiency of H2S is implicated in chronic stress-induced depression. S-adenosylmethionine (SAM) is an agonist of cystathionine β-synthase (CBS), which increases endogenous H2S levels. This present study was designed to investigate the ability of SAM to prevent depression-like behaviors induced by chronic stress and the underlying mechanisms. A mouse model of chronic unpredictable mild stress (CUMS) was adopted to examine the effects of SAM on depression-like behaviors as well as synaptic proteins and synaptic morphology. CUMS induced depression-like behaviors after 2, 4 and 6 weeks as measured by the open field test, sucrose preference test, and forced swimming test. Further, there were significant reductions in endogenous H2S, CBS, and brainderived neurotrophic factor (BDNF) and synapse-associated proteins (synaptophysin, SYN and postsynaptic density protein 95, PSD-95) in the hippocampus of the CUMS group.SAM exposure prevented the effects of CUMS on depressive-like behaviors and the levels of H2S and CBS in the hippocampus. SAM administration also increased BDNF, SYN and PSD-95 in the hippocampus of CUMS mice, and improved the ultrastructure of synapses as examined by electron microscopy. These results demonstrate that SAM exerts antidepressant-like effects in CUMS mice, specifically through enhancing H2S, CBS and neuroplasticity. These findings highlight the novel role of endogenous H2S in mediating antidepressant-like behaviour and its potential for the prevention of chronic stress-induced depression.


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