PMID- 26390937
OWN - NLM
STAT- MEDLINE
DCOM- 20160817
LR  - 20181202
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1627
DP  - 2015 Nov 19
TI  - Exendin-4 antagonizes Abeta1-42-induced suppression of long-term potentiation by 
      regulating intracellular calcium homeostasis in rat hippocampal neurons.
PG  - 101-8
LID - S0006-8993(15)00713-1 [pii]
LID - 10.1016/j.brainres.2015.09.015 [doi]
AB  - An imbalance of intracellular calcium homeostasis induced by amyloid beta-protein 
      (Abeta) contributes to the pathogenesis of Alzheimer's disease (AD), such as 
      deficits in learning and memory. Therefore, regulation of calcium homeostasis may 
      represent a new strategy for treatment of AD. Growing evidence suggests that type 
      2 diabetes mellitus (T2DM) and AD are closely related in pathogenesis. Thus, 
      drugs used in treatment of T2DM may modify the pathogenesis of AD. This study 
      demonstrated that Exendin-4, which is a glucagon-like peptide-1 (GLP-1) analog 
      used as a therapeutic drug for T2DM, significantly antagonized suppression of 
      long-term potentiation (LTP) induced by Abeta1-42 in the rat hippocampal CA1 region 
      in vivo. This neuroprotection may be mediated by regulation of calcium 
      homeostasis. Pretreatment with Exendin-4 suppressed Abeta1-42-induced elevation in 
      intracellular calcium concentration ([Ca(2+)]i) through L-type voltage-dependent 
      calcium channels (L-VDCCs) and N-methyl-D-aspartate receptors (NMDARs). 
      Furthermore, Exendin-4 antagonized the decrease in p-Ca(2+)/calmodulin-dependent 
      protein kinase IIalpha (p-CaMKIIalpha) induced by Abeta1-42 in the rat hippocampal CA1 
      region. Thus, the neuroprotective effects of Exendin-4, which likely involve 
      regulation of calcium homeostasis, provide theoretical support for using 
      Exendin-4 to treat and prevent AD in the future.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Wang, Xiaohui
AU  - Wang X
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China. 
      Electronic address: 163.wangxh@163.com.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Jiang, Ruirui
AU  - Jiang R
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Yuan, Yuan
AU  - Yuan Y
AD  - Morphology Laboratory, Shanxi Medical University, Taiyuan 030001, China.
FAU - Yu, Qianqian
AU  - Yu Q
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Li, Yameng
AU  - Li Y
AD  - Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150921
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 76326-31-3 (2-amino-5-phosphopentanoic acid)
RN  - 9P1872D4OL (Exenatide)
RN  - HG18B9YRS7 (Valine)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amyloid beta-Peptides/pharmacology
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Cells, Cultured
MH  - Electric Stimulation
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Exenatide
MH  - Hippocampus/*cytology
MH  - Homeostasis/drug effects
MH  - Hypoglycemic Agents/*pharmacology
MH  - Long-Term Potentiation/*drug effects
MH  - Microscopy, Confocal
MH  - Neurons/*drug effects
MH  - Nifedipine/pharmacology
MH  - Patch-Clamp Techniques
MH  - Peptide Fragments/pharmacology
MH  - Peptides/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Valine/analogs & derivatives/pharmacology
MH  - Venoms/*pharmacology
OTO - NOTNLM
OT  - Abeta1-42
OT  - Calcium homeostasis
OT  - Exendin-4
OT  - Neuroprotection
EDAT- 2015/09/24 06:00
MHDA- 2016/08/18 06:00
CRDT- 2015/09/23 06:00
PHST- 2015/05/25 00:00 [received]
PHST- 2015/09/06 00:00 [revised]
PHST- 2015/09/11 00:00 [accepted]
PHST- 2015/09/23 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/08/18 06:00 [medline]
AID - S0006-8993(15)00713-1 [pii]
AID - 10.1016/j.brainres.2015.09.015 [doi]
PST - ppublish
SO  - Brain Res. 2015 Nov 19;1627:101-8. doi: 10.1016/j.brainres.2015.09.015. Epub 2015 
      Sep 21.