title: Disturbance of endogenous hydrogen sulfide generation and endoplasmic reticulum stress in hippocampus are involved in homocysteine-induced defect in learning and memory of rats.
abstract: Homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Hydrogen sulfide (H2S) acts as an endogenous neuromodulator and neuroprotectant. It has been shown that endoplasmic reticulum (ER) stress is involved in the pathological mechanisms of the learning and memory dysfunctions and that H2S exerts its neuroprotective role via suppressing ER stress. In the present work, we explored the effects of intracerebroventricular injection of Hcy on the formation of learning and memory, the generation of endogenous H2S, and the expression of ER stress in the hippocampus of rats. We found that intracerebroventricular injection of Hcy in rats leads to learning and memory dysfunctions in the Morris water maze and novel of object recognition test and decreases in the expression of cystathionine-β-synthase, the major enzyme responsible for endogenous H2S generation, and the generation of endogenous H2S in the hippocampus of rats. We also showed that exposure of Hcy could up-regulate the expressions of glucose-regulated protein 78 (GRP78), CHOP, and cleaved caspase-12, which are the major mark proteins of ER stress, in the hippocampus of rats. Taken together, these results suggest that the disturbance of hippocampal endogenous H2S generation and the increase in ER stress in the hippocampus are related to Hcy-induced defect in learning and memory.
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China; Institute of Neuroscience, Medical College, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Man-Hong
authors.initials: MH
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China; Institute of Neuroscience, Medical College, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Tang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Medical College, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China. Electronic address: zouw415@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, PR China; Institute of Neuroscience, Medical College, University of South China, Hengyang, 421001 Hunan, PR China. Electronic address: tangxq01001@foxmail.com.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D006710:Homocysteine; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Endoplasmic reticulum stress; Homocysteine; Hydrogen sulfide; Learning and memory; Morris water maze; Novel object recognition test