H₂S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke.
Neuronal damage in the hippocampal formation which is more sensitive to ischemic stimulation and easily injured will cause severe learning and memory impairment. Therefore, inhibiting hippocampal neuron injuries is the main contributor for learning and memory impairment during cerebral ischemia. Hydrogen sulfide (H2S) is a new type of neurotransmitter that regulates the nervous, circulatory and immune systems as well as various adverse factors that can reduce cerebral vascular or brain parenchyma injury. During an ischemic stroke, H2S inhibits hippocampal neuronal damage, reducing learning and memory impairment. However, this molecular mechanism has not been elucidated clearly. In this study, we established four-vessel occlusion model in rats with cerebral ischemia. We found that NaHS (28 mmol/kg, intraperitoneally, for 7 days before ischemia), donor of H2S, significantly shortened the distance and time of loading onto the hidden platform in the positioning navigation process, decreased the latency in the space exploration process when cognitive testing with Morris water maze was performed during ischemic stroke in rats. NaHS also significantly shortened latency and reduced the number of errors in the platform diving experiment. The survival rate of neurons in the CA1 area of the hippocampus and the phosphorylation of Akt in the neurons were increased, the phosphorylation ASK1 and JNK3 were inhibited by NaHS. After an intracerebroventricular injection of LY294002 (inhibitor of PI3K/Akt, 10 μL, 100 nmol in 25% DMSO in PBS), the above effects of NaHS were attenuated. These findings suggest that H2S may improve the survival rate of hippocampal neurons and reduce the impairment of learning and memory by increasing the phosphorylation of Akt, inhibiting the phosphorylation of ASK1 and JNK3 in rats with induced ischemic stroke.
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China; School of Basic Education Sciences, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Xiangru
X
Wen
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Dashi
D
Qi
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, PR China.
Ying
Y
Sun
School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Xiaojing
X
Huang
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Fang
F
Zhang
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Jian
J
Wu
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Yanyan
Y
Fu
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China; Department of Medical Information, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Kai
K
Ma
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Yang
Y
Du
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China.
Hongyan
H
Dong
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, PR China.
YongHai
Y
Liu
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China. Electronic address: 869133848@qq.com.
Hongzhi
H
Liu
Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu 221004, PR China. Electronic address: biosongyuanjian@126.com.
Yuanjian
Y
Song
D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000150:complications*; D013440:Sulfides / Q000494:pharmacology
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D018696:Neuroprotective Agents; D013440:Sulfides; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D048057:Mitogen-Activated Protein Kinase 10; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
Hippocampal neuron; Hydrogen sulfide; Protein kinase B; Stroke