H2S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke

• Published in: Behavioural brain research Vol. 269; pp. 6 - 14
• Main Authors: Wen, Xiangru, Qi, Dashi, Sun, Ying, Huang, Xiaojing, Zhang, Fang, Wu, Jian, Fu, Yanyan, Ma, Kai, Du, Yang, Dong, Hongyan, Liu, YongHai, Liu, Hongzhi, Song, Yuanjian
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.08.2014; Elsevier
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Brain Ischemia - complications; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - pathology; CA1 Region, Hippocampal - physiopathology; Cell Survival - drug effects; Chromones - pharmacology; Cognition Disorders - drug therapy; Cognition Disorders - etiology; Cognition Disorders - pathology; Cognition Disorders - physiopathology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampal neuron; Hydrogen sulfide; Hydrogen Sulfide - pharmacology; Male; MAP Kinase Kinase Kinase 5 - metabolism; Mitogen-Activated Protein Kinase 10 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 10 - metabolism; Morpholines - pharmacology; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Neuroprotective Agents - pharmacology; Phosphorylation - drug effects; Protein kinase B; Proto-Oncogene Proteins c-akt - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats, Sprague-Dawley; Signal Transduction - drug effects; Stroke; Stroke - complications; Sulfides - pharmacology; Vertebrates: nervous system and sense organs; Hydrogen sulfide; Stroke; Hippocampal neuron; Protein kinase B; Nervous system diseases; Cognitive disorder; Central nervous system; Akt protein kinase; Cardiovascular disease; Encephalon; Cerebral disorder; Vascular disease; Signal transduction; Neuron; Central nervous system disease; Cerebrovascular disease; Hippocampus
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2014.04.027

•Learning and memory impairments observed after brain I/R could be decreased by NaHS.•NaHS could reduce the hippocampal CA1 neuronal injury induced by I/R.•NaHS could inhibit the phosphorylation of ASK1 and JNK3 via phosphorylating Akt1. 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 (28mmol/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, 10μL, 100nmol 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.