title: Sodium Hydrosulfide Attenuates Beta-Amyloid-Induced Cognitive Deficits and Neuroinflammation via Modulation of MAPK/NF-κB Pathway in Rats.
abstract: Beta-amyloid (Aβ), a neurotoxic peptide, accumulates in the brain of Alzheimer's disease (AD) subjects to initiate neuroinflammation eventually leading to memory impairment. Here, we demonstrated that Aβ-injected rats exhibited cognitive impairment and neuroinflammation with a remarkable reduction of hydrogen sulfide (H2S) levels in the hippocampus compared with that in shamoperated rats. Interestingly, the expression of cystathionine-β-synthase (CBS) and 3- mercaptopyruvate-sulfurtransferase (3MST), the major enzymes responsible for endogenous H2S generation, were also significantly decreased. However, intraperitoneal (i.p.) injection of sodium hydrosulfide (NaHS, a H2S donor) dramatically attenuated cognitive impairment and neuroinflammation induced by hippocampal injection of 10 μg of Aβ1-42 in rats. Subsequently, NaHS significantly suppressed the expression of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) in rat hippocampus following Aβ administration. Furthermore, NaHS exerted a beneficial effect on inhibition of IκB-α degradation and subsequent activation of transcription factor nuclear factor κB (NF-κB), as well as inhibition of extracellular signal-regulated kinase (ERK1/2) activity and p38 MAPK activity but not c-Jun N-terminal kinase (JNK) activity induced by Aβ. These results demonstrate that NaHS might be a potential agent for treatment of neuroinflammation-related AD.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Deng
authors.forename: Jianmei
authors.initials: J
authors.lastname: Gao
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenxian
authors.initials: W
authors.lastname: Li
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shi
authors.affiliation: 201 Da Lian Road, Zunyi City, Guizhou Province, 563000, P. R. China. gqh@zmc.edu.cn.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gong
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018697:Nootropic Agents / Q000008:administration & dosage; D010446:Peptide Fragments; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage*; D013466:Sulfurtransferases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; D013440:Sulfides; C075222:amyloid beta-protein (1-42); D013466:Sulfurtransferases; D003541:Cystathionine beta-Synthase; C025451:sodium bisulfide