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

Abstract：

: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.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Wen X,Qi D,Sun Y,Huang X,Zhang F,Wu J,Fu Y,Ma K,Du Y,Dong H,Liu Y,Liu H,Song Y

doi

10.1016/j.bbr.2014.04.027

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

6-14

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(14)00245-9

journal_volume

269

pub_type

杂志文章

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