PMID- 24682776
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20211203
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 29
IP  - 3
DP  - 2014 Sep
TI  - mTOR-mediated hyperphosphorylation of tau in the hippocampus is involved in 
      cognitive deficits in streptozotocin-induced diabetic mice.
PG  - 729-36
LID - 10.1007/s11011-014-9528-1 [doi]
AB  - Abnormal levels of mammalian target of rapamycin (mTOR) signaling have been 
      recently implicated in the pathophysiology of neurodegenerative diseases, such as 
      Alzheimer's disease (AD). However, the implication of mTOR in diabetes mellitus 
      (DM)-related cognitive dysfunction still remains unknown. In the present study, 
      we found that phosphorylated mTOR at Ser2448, phosphorylated p70S6K at 
      Thr421/Ser424 and phosphorylated tau at Ser396 were significantly increased in 
      the hippocampus of streptozotocin (STZ)-induced diabetic mice when compared with 
      control mice. A low dose of rapamycin was used to elucidate the role of mTOR 
      signaling in DM-related cognitive deficit. Rapamycin restored abnormal 
      mTOR/p70S6K signaling and attenuated the phosphorylation of tau protein in the 
      hippocampus of diabetic mice. Furthermore, the spatial learning and memory 
      function of diabetic mice significantly impaired compared with control mice, was 
      also reversed by rapamycin. These findings indicate that mTOR/p70S6K signaling 
      pathway is hyperactive in the hippocampus of STZ-induced diabetic mice and 
      inhibiting mTOR signaling with rapamycin prevents the DM-related cognitive 
      deficits partly through attenuating the hyperphosphorylation of tau protein.
FAU - Wang, Shan
AU  - Wang S
AD  - Department of Pharmaceutical Engineering, College of Chemistry and Chemical 
      Engineering, Central South University, Changsha, China.
FAU - Zhou, Shan-lei
AU  - Zhou SL
FAU - Min, Fang-yuan
AU  - Min FY
FAU - Ma, Jin-ju
AU  - Ma JJ
FAU - Shi, Xia-jie
AU  - Shi XJ
FAU - Bereczki, Erika
AU  - Bereczki E
FAU - Wu, Jing
AU  - Wu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140330
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (tau Proteins)
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  - Animals
MH  - Cognition Disorders/etiology/*metabolism
MH  - Diabetes Mellitus, Experimental/complications/*metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/drug effects/*metabolism
MH  - Maze Learning/drug effects/physiology
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - tau Proteins/*metabolism
EDAT- 2014/04/01 06:00
MHDA- 2015/10/17 06:00
CRDT- 2014/04/01 06:00
PHST- 2014/01/01 00:00 [received]
PHST- 2014/03/07 00:00 [accepted]
PHST- 2014/04/01 06:00 [entrez]
PHST- 2014/04/01 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
AID - 10.1007/s11011-014-9528-1 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2014 Sep;29(3):729-36. doi: 10.1007/s11011-014-9528-1. Epub 2014 
      Mar 30.