PMID- 30632006
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20200801
IS  - 1995-8218 (Electronic)
IS  - 1673-7067 (Print)
IS  - 1995-8218 (Linking)
VI  - 35
IP  - 4
DP  - 2019 Aug
TI  - Liraglutide Ameliorates Hyperhomocysteinemia-Induced Alzheimer-Like Pathology and 
      Memory Deficits in Rats via Multi-molecular Targeting.
PG  - 724-734
LID - 10.1007/s12264-018-00336-7 [doi]
AB  - Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease 
      (AD), and insulin-resistance is commonly seen in patients with Hhcy. Liraglutide 
      (Lir), a glucagon-like peptide that increases the secretion and sensitivity of 
      insulin, has a neurotrophic or neuroprotective effect. However, it is not known 
      whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy. 
      By vena caudalis injection of homocysteine to produce the Hhcy model in rats, we 
      found here that simultaneous administration of Lir for 2 weeks ameliorated the 
      Hhcy-induced memory deficit, along with increased density of dendritic spines and 
      up-regulation of synaptic proteins. Lir also attenuated the Hhcy-induced tau 
      hyperphosphorylation and Abeta overproduction, and the molecular mechanisms involved 
      the restoration of protein phosphatase-2A activity and inhibition of beta- and 
      gamma-secretases. Phosphorylated insulin receptor substrate-1 also decreased after 
      treatment with Lir. Our data reveal that Lir improves the Hhcy-induced AD-like 
      spatial memory deficit and the mechanisms involve the modulation of 
      insulin-resistance and the pathways generating abnormal tau and Abeta.
FAU - Zhang, Yao
AU  - Zhang Y
AD  - Endocrinology Department of Liyuan Hospital and Key Laboratory of the Ministry of 
      Education of China for Neurological Disorders, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Xie, Jia-Zhao
AU  - Xie JZ
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of the Ministry of Education 
      of China for Neurological Disorders, Tongji Medical College, Huazhong University 
      of Science and Technology, Wuhan, 430030, China.
FAU - Xu, Xiang-Yang
AU  - Xu XY
AD  - Radiology Department, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Hu, Jun
AU  - Hu J
AD  - Endocrinology Department, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Xu, Teng
AU  - Xu T
AD  - Endocrinology Department, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Jin, Si
AU  - Jin S
AD  - Endocrinology Department, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Yang, Shao-Juan
AU  - Yang SJ
AD  - Endocrinology Department, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Wang, Jian-Zhi
AU  - Wang JZ
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of the Ministry of Education 
      of China for Neurological Disorders, Tongji Medical College, Huazhong University 
      of Science and Technology, Wuhan, 430030, China. wangjz@mail.hust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190110
PL  - Singapore
TA  - Neurosci Bull
JT  - Neuroscience bulletin
JID - 101256850
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 0 (tau Proteins)
RN  - 839I73S42A (Liraglutide)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/*etiology/metabolism/pathology
MH  - Amyloid beta-Peptides
MH  - Animals
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/metabolism
MH  - Hyperhomocysteinemia/chemically induced/*drug therapy/metabolism/pathology
MH  - Insulin Resistance
MH  - Liraglutide/*pharmacology/*therapeutic use
MH  - Male
MH  - Maze Learning
MH  - Memory Disorders/drug therapy
MH  - Neuronal Plasticity
MH  - Neuroprotective Agents/pharmacology
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Neurotransmitter
MH  - tau Proteins/metabolism
PMC - PMC6616622
OTO - NOTNLM
OT  - Glucagon-like peptide-1 receptor
OT  - Hyperhomocysteinemia
OT  - Liraglutide
OT  - Tau
OT  - beta-Amyloid
COIS- The authors claim that there are no conflicts of interest.
EDAT- 2019/01/12 06:00
MHDA- 2020/02/19 06:00
PMCR- 2020/08/01
CRDT- 2019/01/12 06:00
PHST- 2018/07/26 00:00 [received]
PHST- 2018/09/17 00:00 [accepted]
PHST- 2019/01/12 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2019/01/12 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - 10.1007/s12264-018-00336-7 [pii]
AID - 336 [pii]
AID - 10.1007/s12264-018-00336-7 [doi]
PST - ppublish
SO  - Neurosci Bull. 2019 Aug;35(4):724-734. doi: 10.1007/s12264-018-00336-7. Epub 2019 
      Jan 10.