title: The PI3K-AKT-mTOR pathway activates recovery from general anesthesia.
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.
authors.affiliation: Department of Anesthesia, the Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Chifeng Municipal Hospital, Chifeng, P. R. China.
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Song
authors.affiliation: Department of Anesthesia, the Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Anesthesia, the Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Cai
authors.affiliation: Department of Anesthesia, Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesia, the Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Jin-Gui
authors.initials: JG
authors.lastname: Gao
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D007649:Ketamine / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D023421:Models, Animal; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D065853:Spatial Learning / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007649:Ketamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C546845:mTOR protein, rat
keywords: PI3K-AKT-mTOR pathway; Pathology Section; general anesthesia; morris water maze; recovery from general anesthesia; righting reflex