PMID- 31306126
OWN - NLM
STAT- MEDLINE
DCOM- 20201009
LR  - 20211204
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 70
IP  - 3
DP  - 2019
TI  - Intranasal Insulin Increases Synaptic Protein Expression and Prevents 
      Anesthesia-Induced Cognitive Deficits Through mTOR-eEF2 Pathway.
PG  - 925-936
LID - 10.3233/JAD-190280 [doi]
AB  - General anesthesia increases the risk for cognitive impairment and Alzheimer's 
      disease (AD) in vulnerable individuals such as the elderly. We previously 
      reported that prior administration of insulin through intranasal delivery can 
      prevent the anesthesia-induced cognitive impairment and biochemical changes in 
      the brain. However, little is known about the underlying molecular mechanisms. 
      Here, we report that general anesthesia resulted in downregulation of 
      mammalian/mechanistic target of rapamycin (mTOR) and eukaryotic elongation factor 
      2 (eEF2) in the brain along with reduction of presynaptic proteins and 
      brain-derived neurotrophic factor and cognitive impairment in aged mice. Prior 
      administration of intranasal insulin prevented these anesthesia-induced changes. 
      These results suggest the involvement of the mTOR-eEF2 signaling pathway in the 
      anesthesia-induced brain changes and cognitive impairment and in the prevention 
      of these changes with insulin. Correlation analyses and the use of eEF2 kinase 
      inhibitor further support our conclusions. These studies shed light on the 
      molecular mechanism by which anesthesia and insulin could act on synaptic 
      proteins and cognitive function.
FAU - Yu, Qian
AU  - Yu Q
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
AD  - Department of Orthopedics, Qianfoshan Hospital, Shandong University, Jinan, 
      China.
FAU - Dai, Chun-Ling
AU  - Dai CL
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
FAU - Zhang, Yongli
AU  - Zhang Y
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
FAU - Chen, Yanxing
AU  - Chen Y
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
AD  - Department of Neurology, the Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Wu, Zhe
AU  - Wu Z
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
AD  - Department of Cell Biology and Genetics, School of Basic Medical College, Hubei 
      University of Science and Technology, Xianning, Hubei, China.
FAU - Iqbal, Khalid
AU  - Iqbal K
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
FAU - Liu, Fei
AU  - Liu F
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
FAU - Gong, Cheng-Xin
AU  - Gong CX
AD  - Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State 
      Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.20 (Eef2k protein, mouse)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
SB  - IM
MH  - Administration, Intranasal
MH  - *Alzheimer Disease/metabolism/psychology
MH  - Anesthesia, General/adverse effects
MH  - Animals
MH  - Brain/*metabolism
MH  - Cognition/drug effects
MH  - *Cognitive Dysfunction/etiology/metabolism/prevention & control
MH  - *Elongation Factor 2 Kinase/antagonists & inhibitors/metabolism
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/*pharmacology
MH  - Mice
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Anesthesia
OT  - cognitive impairment
OT  - eEF2
OT  - insulin
OT  - intranasal delivery
OT  - mTOR
OT  - synaptic proteins
EDAT- 2019/07/16 06:00
MHDA- 2020/10/10 06:00
CRDT- 2019/07/16 06:00
PHST- 2019/07/16 06:00 [pubmed]
PHST- 2020/10/10 06:00 [medline]
PHST- 2019/07/16 06:00 [entrez]
AID - JAD190280 [pii]
AID - 10.3233/JAD-190280 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2019;70(3):925-936. doi: 10.3233/JAD-190280.