Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats.
The mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6k) pathway exerts anti‑apoptotic effects that may contribute to disease pathogenesis. The memory impairment in patients with Alzheimer's disease (AD) has been suggested to be contributed to by abnormal mTOR signaling. The aim of the current study was to investigate the association between sevoflurane and/or surgery and AD through the mTOR/p70S6K signaling pathway. Sprague‑Dawley rats were randomly assigned to the sevoflurane, surgery or control groups. The animals in the surgery group received a partial hepatectomy under sevoflurane anesthesia. The hippocampal levels of phosphorylated (p)‑mTOR, p‑p70S6K, caspase‑3 and p‑tau/total (t)‑tau were analyzed. The Morris water maze (MWM) was used to evaluate cognitive function following treatment. The levels of p‑mTOR and p‑p70S6K were reduced, whereas caspase‑3 levels were increased in the surgery group compared with the sevoflurane group. The p‑tau/t‑tau levels were increased, however, tau mRNA was unaffected by sevoflurane and/or surgery. The rats in the surgery group required a significantly longer time to locate the platform in the MWM test compared with the control and sevoflurane groups. Sevoflurane treatment and/or surgery reduced anti‑apoptotic activity, and the postoperative cognitive dysfunction following surgery may be due to mTOR signaling pathway inhibition in aged rats. Increased neuronal apoptosis and tau phosphorylation are suggested to be involved in the association between anesthesia and AD occurrence.
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Yongzhe
Y
Liu
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Li
L
Ma
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Linbo
L
Jiao
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Minglong
M
Gao
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Wenzhi
W
Guo
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Lin
L
Chen
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Ningling
N
Pan
Department of Anesthesiology, Beijing Military General Hospital, Beijing 100700, P.R. China.
Yaqun
Y
Ma
D000777:Anesthetics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects; D006624:Hippocampus / Q000378:metabolism; D018782:Maze Learning; D008738:Methyl Ethers / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D000777:Anesthetics; C489131:Mapt protein, rat; D008738:Methyl Ethers; D016875:tau Proteins; D000077149:Sevoflurane; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases