Oncotarget

Research Papers: Pathology:

The PI3K-AKT-mTOR pathway activates recovery from general anesthesia

Yun-Hui Zhang, Jin Zhang, Jian-Nan Song, Xue Xu, Jin-Song Cai, Yang Zhou and Jin-Gui Gao _

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Oncotarget. 2016; 7:40939-40952. https://doi.org/10.18632/oncotarget.10172

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Abstract

Yun-Hui Zhang1, Jin Zhang2, Jian-Nan Song3, Xue Xu1, Jin-Song Cai1, Yang Zhou4 and Jin-Gui Gao1

1 Department of Anesthesia, the Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China

2 Department of Anesthesia, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, P. R. China

3 Department of Anesthesia, Chifeng Municipal Hospital, Chifeng, P. R. China

4 Department of Anesthesia, Hebei Medical University, Shijiazhuang, P. R. China

Correspondence to:

Jin-Gui Gao, email:

Keywords: PI3K-AKT-mTOR pathway, general anesthesia, recovery from general anesthesia, righting reflex, morris water maze, Pathology Section

Received: February 17, 2016 Accepted: May 16, 2016 Published: June 19, 2016

Abstract

We investigated roles of PI3K-AKT-mTOR pathway in recovery from general anesthesia. Sprague-Dawley rats divided into five groups: saline+artificial cerebrospinal fluid (ACSF; Group A), ketamine+ACSF (Group B), ketamine+IGF-1 (Group C), ketamine+PI3K inhibitor (Group D), and PI3K/Akt agonists (Group E). Proportion of δ waves on ECoGs was recorded. Rats were tested for duration of loss of righting reflex (LORR), ataxic period and behavior in Morris water maze. mRNA and protein expression of members of PI3K-AKT-mTOR pathway were measured by RT-qPCR and Western blots. Histopathologic changes in hippocampal tissues observed by HE staining. We found that the proportion of δ waves decreased in Group C, while increased in Group D compared with Group B; the durations of LORR and ataxic period were shorter in Group C, but longer in Group D. In Morris water maze, escape latency (EL) and duration and frequency of staying on platform was shorter in Group C and longer in Group D than in Group B. Group A exhibited low expression of proteins in PI3K-AKT-mTOR pathway, while p-AKT, p-mTOR and p-P70S6K expression increased in cerebral cortex, brain stem, and thalamus in Group C. By contrast, expression of those proteins was lower in Group D than Group B. Those proteins expressions were higher in Group E than in Group A. HE staining showed that anesthesia may induce cell apoptosis in rat hippocampal CA1 areas, and PI3K/Akt agonists could inhibit apoptosis. Our results suggest that activation of PI3K-AKT-mTOR pathway may promote recovery from general anesthesia and enhance spatial learning and memory.


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