PMID- 31865521
OWN - NLM
STAT- MEDLINE
DCOM- 20201117
LR  - 20211204
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 45
IP  - 2
DP  - 2020 Feb
TI  - Autophagy Dysfunction and mTOR Hyperactivation Is Involved in Surgery: Induced 
      Behavioral Deficits in Aged C57BL/6J Mice.
PG  - 331-344
LID - 10.1007/s11064-019-02918-x [doi]
AB  - Autophagy is crucial for cell survival, development, division, and homeostasis. 
      The mammalian target of rapamycin (mTOR), which is the foremost negative 
      controller of autophagy, plays a key role in many endogenous processes. The 
      present study investigated whether rapamycin can ameliorate surgery-induced 
      cognitive deficits by inhibiting mTOR and activating autophagy in the 
      hippocampus. Both adult and aged C57BL/6J mice received an intraperitoneal 
      injection of rapamycin (10 mg/kg/day) for 5 days per week for one and a half 
      months. Mice were then subjected to partial hepatectomy under general anesthesia. 
      Behavioral performance was assessed on postoperative days 3, 7, and 14. 
      Hippocampal autophagy-related (Atg)-5, phosphorylated mTOR, and phosphorylated 
      p70S6K were examined at each time point. Brain derived neurotrophic factor 
      (BDNF), synaptophysin, and tau hyperphosphorylation (T396) in the hippocampus 
      were also examined. Surgical trauma and anesthesia exacerbated spatial learning 
      and memory impairment in aged mice on postoperative days 3 and 7. Following 
      partial hepatectomy, the levels of phosphorylated mTOR, phosphorylated 70S6K, and 
      phosphorylated tau were all increased in the hippocampus. A corresponding decline 
      in BDNF and synaptophysin were observed. Rapamycin treatment restored autophagy 
      function, attenuated phosphorylation of tau protein, and increased BDNF and 
      synaptophysin expression in the hippocampus of surgical mice. Furthermore, 
      surgery and anesthesia induced spatial learning and memory impairments were also 
      reversed by rapamycin treatment. Autophagy impairments and mTOR hyperactivation 
      were detected along with surgery-induced behavioral deficits. Inhibiting the mTOR 
      signaling pathway with rapamycin successfully ameliorated surgery-related 
      cognitive impairments by sustaining autophagic degradation, inhibiting tau 
      hyperphosphorylation, and increasing synaptophysin and BDNF expression.
FAU - Jiang, Yanhua
AU  - Jiang Y
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Zhou, Yongjian
AU  - Zhou Y
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Ma, Hong
AU  - Ma H
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China. mahong5466@yahoo.com.
FAU - Cao, Xuezhao
AU  - Cao X
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Li, Zhe
AU  - Li Z
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Chen, Fengshou
AU  - Chen F
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Wang, Hongnan
AU  - Wang H
AD  - Department of Anesthesiology, The First Hospital of China Medical University, 
      Shenyang, Liaoning, China.
LA  - eng
PT  - Journal Article
DEP - 20191221
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Neuroprotective Agents)
RN  - 38LVP0K73A (Sevoflurane)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Autophagy/*physiology
MH  - Hepatectomy/*adverse effects
MH  - Hippocampus/metabolism
MH  - Liver/surgery
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*therapeutic use
MH  - Postoperative Cognitive Complications/etiology/*prevention & control
MH  - Sevoflurane/adverse effects
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - Aged
OT  - Autophagy
OT  - Behavioral deficits
OT  - Surgery-induced
OT  - mTOR
EDAT- 2019/12/23 06:00
MHDA- 2020/11/18 06:00
CRDT- 2019/12/23 06:00
PHST- 2019/03/14 00:00 [received]
PHST- 2019/11/22 00:00 [accepted]
PHST- 2019/10/29 00:00 [revised]
PHST- 2019/12/23 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/12/23 06:00 [entrez]
AID - 10.1007/s11064-019-02918-x [pii]
AID - 10.1007/s11064-019-02918-x [doi]
PST - ppublish
SO  - Neurochem Res. 2020 Feb;45(2):331-344. doi: 10.1007/s11064-019-02918-x. Epub 2019 
      Dec 21.