PMID- 29050859
OWN - NLM
STAT- MEDLINE
DCOM- 20180302
LR  - 20181024
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1678
DP  - 2018 Jan 1
TI  - Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the 
      APP/PS1 transgenic mouse model of Alzheimer's disease.
PG  - 64-74
LID - S0006-8993(17)30459-6 [pii]
LID - 10.1016/j.brainres.2017.10.012 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). 
      Previous studies have shown that the incretin hormones glucagon-like peptide-1 
      (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) that have 
      anti-diabetic properties show very promising effects in animal models of AD. 
      Glucagon (Gcg) is a hormone and growth-factor, and the Gcg receptor is expressed 
      in the brain. Here we test the effects of a triple receptor agonist (TA), which 
      activates GIP-1, GIP and glucagon receptors at the same time. In the present 
      study, the effects of the TA were evaluated in the APP/PS1 transgenic mouse model 
      of AD. The TA was injected once-daily (10 nmol/kg i.p.) for two months. The 
      results showed that treatment with TA significantly reversed the memory deficit 
      in the APP/PS1 mice in a spatial water maze test. Moreover, the drug reduced 
      levels of the mitochondrial pro-apoptotic signaling molecule BAX, increased the 
      anti-apoptotic signaling molecule Bcl-2 and enhanced the levels of BDNF, a key 
      growth factor that protects synaptic function. Levels of synaptophysin were 
      enhanced, demonstrating protection from synaptic loss that is observed in AD. 
      Neurogenesis in the dentate gyrus was furthermore enhanced as shown in the 
      increase of doublecortin positive cells. Furthermore, TA treatment reduced the 
      total amount of beta-amyloid, reduced neuroinflammation (activated microglia and 
      astrocytes), and oxidative stress in the cortex and hippocampus. Thus, these 
      findings show that novel TAs are a promising lead for the design of future 
      treatment strategies in AD.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Tai, Jingjing
AU  - Tai J
AD  - Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 
      Shanxi, PR China.
FAU - Liu, Weizhen
AU  - Liu W
AD  - Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 
      Shanxi, PR China.
FAU - Li, Yanwei
AU  - Li Y
AD  - Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 
      Shanxi, PR China; Department of Human Anatomy, Medical College, Shaoyang 
      University, Shaoyang, Hunan, PR China.
FAU - Li, Lin
AU  - Li L
AD  - Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 
      Shanxi, PR China. Electronic address: linlilin999@163.com.
FAU - Holscher, Christian
AU  - Holscher C
AD  - Second Hospital Neurology Dept., Shanxi Medical University, Taiyuan, Shanxi, PR 
      China; Biomedical and Life Science, Faculty of Health and Medicine, Lancaster 
      University, Lancaster LA1 4YQ, UK.
LA  - eng
PT  - Journal Article
DEP - 20171016
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Presenilin-1)
RN  - 0 (Receptors, Gastrointestinal Hormone)
RN  - 0 (Receptors, Glucagon)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
RN  - D6H00MV7K8 (gastric inhibitory polypeptide receptor)
SB  - IM
MH  - Alzheimer Disease/drug therapy/physiopathology
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Disease Models, Animal
MH  - Glucagon/pharmacology
MH  - Glucagon-Like Peptide 1/pharmacology
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism
MH  - Hippocampus/metabolism
MH  - Memory Disorders/drug therapy
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroprotective Agents/*metabolism/pharmacology
MH  - Plaque, Amyloid/drug therapy
MH  - Presenilin-1/metabolism
MH  - Receptors, Gastrointestinal Hormone/*agonists/metabolism
MH  - Receptors, Glucagon/*agonists/metabolism
OTO - NOTNLM
OT  - BDNF
OT  - Brain
OT  - Growth factor
OT  - Inflammation
OT  - Insulin
OT  - Neurodegeneration
EDAT- 2017/10/21 06:00
MHDA- 2018/03/03 06:00
CRDT- 2017/10/21 06:00
PHST- 2017/07/05 00:00 [received]
PHST- 2017/10/07 00:00 [revised]
PHST- 2017/10/11 00:00 [accepted]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2018/03/03 06:00 [medline]
PHST- 2017/10/21 06:00 [entrez]
AID - S0006-8993(17)30459-6 [pii]
AID - 10.1016/j.brainres.2017.10.012 [doi]
PST - ppublish
SO  - Brain Res. 2018 Jan 1;1678:64-74. doi: 10.1016/j.brainres.2017.10.012. Epub 2017 
      Oct 16.