PMID- 33140268
OWN - NLM
STAT- MEDLINE
DCOM- 20210809
LR  - 20240226
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 46
IP  - 2
DP  - 2021 Feb
TI  - Rapamycin Ameliorates Cognitive Impairments and Alzheimer's Disease-Like 
      Pathology with Restoring Mitochondrial Abnormality in the Hippocampus of 
      Streptozotocin-Induced Diabetic Mice.
PG  - 265-275
LID - 10.1007/s11064-020-03160-6 [doi]
AB  - Alzheimer's disease (AD) and diabetes mellitus (DM) share common 
      pathophysiological findings, in particular, the mammalian target of rapamycin 
      (mTOR) has been strongly implied to link to AD, while it also plays a key role in 
      the insulin signaling pathway. However, the mechanism of how DM and AD is coupled 
      remains elusive. In the present study, we found that streptozotocin (STZ)-induced 
      DM mice significantly increased the levels P-mTOR Ser2448, P-p70S6K Thr389, P-tau 
      Ser356 and Abeta levels (Abeta oligomer/monomer), as well as the levels of Drp1 and 
      p-Drp1 S616 (mitochondrial fission proteins) are increased, whereas no change was 
      found in the expression of Opa1, Mfn1 and Mfn2 (mitochondrial fusion proteins) 
      compared with control mice. Moreover, the expression of 4-HNE and 8-OHdG showed 
      an aberrant increase in the hippocampus of STZ-induced DM mice that is associated 
      with a decreased capacity of spatial memory and a loss of synapses. Rapamycin, an 
      inhibitor of mTOR, rescued the STZ-induced increases in mTOR/p70S6K activities, 
      tau phosphorylation and Abeta levels, as well as mitochondria abnormality and 
      cognitive impairment in mice. These findings imply that rapamycin prevents 
      cognitive impairment and protects hippocampus neurons from AD-like pathology and 
      mitochondrial abnormality, and also that rapamycin treatment could normalize 
      these STZ-induced alterations by decreasing hippocampus mTOR/p70S6K 
      hyperactivity.
FAU - Ding, Yuanting
AU  - Ding Y
AD  - Department of Clinical Research Center, The First Affliated Hospital of Guizhou 
      University of Traditional Chinese Medicine, Baoshan Road No.71, Guiyang, 550001, 
      Guizhou, China.
FAU - Liu, Heng
AU  - Liu H
AD  - Department of Anesthesiology, Tongren Municipal People's Hospital, Tongren, 
      554300, Guizhou, China.
FAU - Cen, Mofei
AU  - Cen M
AD  - Department of Clinical Research Center, The First Affliated Hospital of Guizhou 
      University of Traditional Chinese Medicine, Baoshan Road No.71, Guiyang, 550001, 
      Guizhou, China.
FAU - Tao, Yuxiang
AU  - Tao Y
AD  - Department of Clinical Research Center, The First Affliated Hospital of Guizhou 
      University of Traditional Chinese Medicine, Baoshan Road No.71, Guiyang, 550001, 
      Guizhou, China.
FAU - Lai, Chencen
AU  - Lai C
AD  - Department of Clinical Research Center, The First Affliated Hospital of Guizhou 
      University of Traditional Chinese Medicine, Baoshan Road No.71, Guiyang, 550001, 
      Guizhou, China.
FAU - Tang, Zhi
AU  - Tang Z
AUID- ORCID: 0000-0002-6506-9290
AD  - Department of Clinical Research Center, The First Affliated Hospital of Guizhou 
      University of Traditional Chinese Medicine, Baoshan Road No.71, Guiyang, 550001, 
      Guizhou, China. tangzhi_2000@hotmail.com.
LA  - eng
GR  - 81560241/National Natural Science Foundation of China/
GR  - 81960265/National Natural Science Foundation of China/
GR  - [2017]1014/Guizhou Science and Technology Department/
GR  - LH [2017]7156/Guizhou Science and Technology Department/
GR  - [2018]1009/Guizhou Science and Technology Department/
GR  - [2018]5752/Guizhou Science and Technology Department/
GR  - [2020]1Y354/Guizhou Science and Technology Department/
GR  - [2019]9-2-7/Science and Technology Bureau, Guiyang Municipal Government/
GR  - KY [2016]035/Department of Education of Guizhou Province/
PT  - Journal Article
DEP - 20201102
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Mapt protein, mouse)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 0 (tau Proteins)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Cognitive Dysfunction/*drug therapy/etiology/pathology
MH  - Diabetes Mellitus, Experimental/chemically induced/complications/*drug 
      therapy/pathology
MH  - Hippocampus/*drug effects/pathology
MH  - Male
MH  - Memory/drug effects
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*drug effects
MH  - Neuroprotective Agents/*therapeutic use
MH  - Oxidative Stress/drug effects
MH  - Peptide Fragments/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*therapeutic use
MH  - Streptozocin
MH  - Synapses/drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - tau Proteins/metabolism
MH  - Mice
OTO - NOTNLM
OT  - Amyloid-beta
OT  - Cognitive deficit
OT  - Diabetes mellitus
OT  - Mitochondrial abnormality
OT  - Tau hyperphosphorylation
OT  - mTOR/p70S6K
EDAT- 2020/11/04 06:00
MHDA- 2021/08/10 06:00
CRDT- 2020/11/03 05:49
PHST- 2020/04/26 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2020/10/22 00:00 [revised]
PHST- 2020/11/04 06:00 [pubmed]
PHST- 2021/08/10 06:00 [medline]
PHST- 2020/11/03 05:49 [entrez]
AID - 10.1007/s11064-020-03160-6 [pii]
AID - 10.1007/s11064-020-03160-6 [doi]
PST - ppublish
SO  - Neurochem Res. 2021 Feb;46(2):265-275. doi: 10.1007/s11064-020-03160-6. Epub 2020 
      Nov 2.