PMID- 24583037
OWN - NLM
STAT- MEDLINE
DCOM- 20150608
LR  - 20161125
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 277
DP  - 2014 Sep 26
TI  - Lixisenatide rescues spatial memory and synaptic plasticity from amyloid beta 
      protein-induced impairments in rats.
PG  - 6-13
LID - S0306-4522(14)00133-X [pii]
LID - 10.1016/j.neuroscience.2014.02.022 [doi]
AB  - Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied 
      by cognitive impairment, but effective strategies against AD are currently not 
      available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes 
      mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. 
      Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half 
      life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, 
      the neuroprotective effects of lixisenatide in the brain remain to be clarified. 
      In the present study, we report for the first time the effects of lixisenatide on 
      the amyloid beta (Abeta) protein-induced impairments in spatial learning and memory of 
      rats, and investigated its electrophysiological and molecular mechanisms. We 
      found that: (1) bilateral intrahippocampal injection of Abeta25-35 resulted in a 
      significant decline in spatial learning and memory of rats, as well as a 
      suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide 
      treatment effectively prevented the Abeta25-35-induced impairments; (3) lixisenatide 
      inhibited the Abeta25-35 injection-induced activation of glycogen synthase kinase 3beta 
      (GSK3beta), with a significant increase in the phosphorylation of ser9 and a 
      significant decrease in the phosphorylation of Y216. These results indicate that 
      lixisenatide, by affecting the PI3K-Akt-GSK3beta pathway, can prevent Abeta-related 
      impairments in synaptic plasticity and spatial memory of rats, suggesting that 
      lixisenatide may be a novel and effective treatment for AD.
CI  - Copyright (c) 2014. Published by Elsevier Ltd.
FAU - Cai, H-Y
AU  - Cai HY
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Holscher, C
AU  - Holscher C
AD  - Division of Biomed and Life Sciences, Faculty of Health and Medicine Lancaster 
      University, Lancaster LA1 4YQ, UK.
FAU - Yue, X-H
AU  - Yue XH
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Zhang, S-X
AU  - Zhang SX
AD  - Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China.
FAU - Wang, X-H
AU  - Wang XH
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Qiao, F
AU  - Qiao F
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Yang, W
AU  - Yang W
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Qi, J-S
AU  - Qi JS
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. 
      Electronic address: jinshunqi2006@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140227
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Glp1r protein, rat)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (amyloid beta-protein (25-35))
RN  - 74O62BB01U (lixisenatide)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Alzheimer Disease/drug therapy/physiopathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Disease Models, Animal
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hippocampus/drug effects/physiopathology
MH  - Long-Term Potentiation/*drug effects/physiology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Memory Disorders/*drug therapy/physiopathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Peptide Fragments/*metabolism
MH  - Peptides/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucagon/agonists/metabolism
MH  - Spatial Memory/*drug effects/physiology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Morris water maze
OT  - amyloid beta-protein
OT  - glycogen synthase kinase 3beta
OT  - lixisenatide
OT  - long-term potentiation
EDAT- 2014/03/04 06:00
MHDA- 2015/06/09 06:00
CRDT- 2014/03/04 06:00
PHST- 2014/01/18 00:00 [received]
PHST- 2014/02/15 00:00 [revised]
PHST- 2014/02/18 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2015/06/09 06:00 [medline]
AID - S0306-4522(14)00133-X [pii]
AID - 10.1016/j.neuroscience.2014.02.022 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Sep 26;277:6-13. doi: 10.1016/j.neuroscience.2014.02.022. Epub 
      2014 Feb 27.