• Yuan-Jian Yang, Ying Zhao, Bin Yu, Guo-Gang Xu, Wei Wang, Jin-Qiong Zhan, Zhen-Yu Tang, Ting Wang, and Bo Wei.
• Department of Psychiatry, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China; Medical Experimental Center, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China.
• Neuroscience. 2016 Oct 29; 335: 170-83.

AbstractAlzheimer's disease (AD) is the most common type of clinical dementia. Previous studies have demonstrated that hydrogen sulfide (H2S) is implicated with the pathology of AD, and exogenous H2S attenuates spatial memory impairments in AD animal models. However, the molecular mechanism by which H2S improves cognition in AD has not been fully explored. Here, we report that chronic administration of sodium hydrosulfide (NaHS, a H2S donor) elevated hippocampal H2S levels and enhanced hippocampus-dependent contextual fear memory and novel object recognition in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. In parallel with these behavioral results, treating transgenic mice with NaHS reversed impaired hippocampal long-term potentiation (LTP), which is deemed as the neurobiological basis of learning and memory. At the molecular level, we found that treatment with NaHS did not affect the expression of the GluN1 and GluN2A subunits of NMDA receptor (NMDAR), but did prevent the downregulation of GluN2B subunit and restored its synaptic abundance, response and downstream signaling in the hippocampus in transgenic mice. Moreover, applying Ro 25-6981, a specific GluN2B antagonist, abolished the beneficial effects of NaHS on cognitive performance and hippocampal LTP in transgenic mice. Collectively, our results indicate that H2S can reverse cognitive and synaptic plasticity deficits in AD model mice by restoring surface GluN2B expression and the function of GluN2B-containing NMDARs.Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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