title: GluN2B-containing NMDA receptors contribute to the beneficial effects of hydrogen sulfide on cognitive and synaptic plasticity deficits in APP/PS1 transgenic mice.
abstract: Alzheimer'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.
authors: 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.
authors: Yuan-Jian
authors: YJ
authors: Yang
authors: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors: Ying
authors: Y
authors: Zhao
authors: Medical Experimental Center, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China.
authors: Bin
authors: B
authors: Yu
authors: Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853, PR China.
authors: Guo-Gang
authors: GG
authors: Xu
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors: Wei
authors: W
authors: Wang
authors: Medical Experimental Center, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China.
authors: Jin-Qiong
authors: JQ
authors: Zhan
authors: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors: Zhen-Yu
authors: ZY
authors: Tang
authors: Department of Pharmacology, College of Medical Science, Three Gorges University, Yichang 443002, PR China. Electronic address: tingting0301@126.com.
authors: Ting
authors: T
authors: Wang
authors: Department of Psychiatry, Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang University, Nanchang 330029, PR China. Electronic address: jxmh_wb@163.com.
authors: Bo
authors: B
authors: Wei
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; C121001:NR2B NMDA receptor; D053764:Presenilin-1; D016194:Receptors, N-Methyl-D-Aspartate; C580804:presenilin 1, mouse; D006862:Hydrogen Sulfide
keywords: Alzheimer’s disease; GluN2B-containing NMDARs; cognition; hydrogen sulfide; synaptic plasticity