PMID- 31256135
OWN - NLM
STAT- MEDLINE
DCOM- 20201009
LR  - 20201009
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 70
IP  - 3
DP  - 2019
TI  - Exenatide Reverts the High-Fat-Diet-Induced Impairment of BDNF Signaling and 
      Inflammatory Response in an Animal Model of Alzheimer's Disease.
PG  - 793-810
LID - 10.3233/JAD-190237 [doi]
AB  - Alzheimer's disease (AD) is a multifactorial condition in which, along with 
      amyloid-beta (Abeta) and tau-related pathology, the synergistic activity of 
      co-morbidity factors promote the onset and progression of the disease. 
      Epidemiological evidence indicates that glucose intolerance, deficits in insulin 
      secretion, or type-2 diabetes mellitus (T2DM) participate in increasing cognitive 
      impairment or dementia risk. Insulin plays a pivotal role in the process as the 
      hormone critically regulates brain functioning. GLP-1, the glucagon-like peptide 
      1, facilitates insulin signaling, regulates glucose homeostasis, and modulates 
      synaptic plasticity. Exenatide is a synthetic GLP-1 analog employed in T2DM. 
      However, exenatide has also been shown to affect the signaling of the 
      brain-derived neurotrophic factor (BDNF), synaptic plasticity, and cognitive 
      performances in animal models. In this study, we tested whether exenatide exerts 
      neuroprotection in a preclinical AD model set to mimic the clinical complexity of 
      the human disease. We investigated the effects of exenatide treatment in 3xTg-AD 
      mice challenged with a high-fat diet (HFD). Endpoints of the study were 
      variations in systemic metabolism, insulin and neurotrophic signaling, 
      neuroinflammation, Abeta and tau pathology, and cognitive performances. Results of 
      the study indicate that exenatide reverts the adverse changes of BDNF signaling 
      and the neuroinflammation status of 3xTg-AD mice undergoing HFD without affecting 
      systemic metabolism or promoting changes in cognitive performances.
FAU - Bomba, Manuela
AU  - Bomba M
AD  - Center of Excellence on Aging and Translational Medicine - CeSI-MeT, University 
      G. d'Annunzio of Chieti-Pescara, Italy.
AD  - Department of Neuroscience, Imaging, and Clinical Sciences, University G. 
      d'Annunzio of Chieti-Pescara, Italy.
FAU - Granzotto, Alberto
AU  - Granzotto A
AD  - Center of Excellence on Aging and Translational Medicine - CeSI-MeT, University 
      G. d'Annunzio of Chieti-Pescara, Italy.
AD  - Department of Neuroscience, Imaging, and Clinical Sciences, University G. 
      d'Annunzio of Chieti-Pescara, Italy.
FAU - Castelli, Vanessa
AU  - Castelli V
AD  - Department of Life, Health and Environmental Sciences, University of L'Aquila, 
      Italy.
FAU - Onofrj, Marco
AU  - Onofrj M
AD  - Center of Excellence on Aging and Translational Medicine - CeSI-MeT, University 
      G. d'Annunzio of Chieti-Pescara, Italy.
AD  - Department of Neuroscience, Imaging, and Clinical Sciences, University G. 
      d'Annunzio of Chieti-Pescara, Italy.
FAU - Lattanzio, Rossano
AU  - Lattanzio R
AD  - Center of Excellence on Aging and Translational Medicine - CeSI-MeT, University 
      G. d'Annunzio of Chieti-Pescara, Italy.
AD  - Department of Medical, Oral, and Biotechnological Sciences, University G. 
      d'Annunzio of Chieti-Pescara, Italy.
FAU - Cimini, Annamaria
AU  - Cimini A
AD  - Department of Life, Health and Environmental Sciences, University of L'Aquila, 
      Italy.
AD  - Sbarro Institute for Cancer Research and Molecular Medicine and Center for 
      Biotechnology, Temple University, Philadelphia, PA, USA.
AD  - National Institute for Nuclear Physics (INFN), Gran Sasso National Laboratory 
      (LNGS), Assergi, Italy.
FAU - Sensi, Stefano L
AU  - Sensi SL
AD  - Center of Excellence on Aging and Translational Medicine - CeSI-MeT, University 
      G. d'Annunzio of Chieti-Pescara, Italy.
AD  - Department of Neuroscience, Imaging, and Clinical Sciences, University G. 
      d'Annunzio of Chieti-Pescara, Italy.
AD  - Departments of Neurology and Pharmacology, Institute for Mind Impairments and 
      Neurological Disorders - iMIND, University of California - Irvine, Irvine, CA, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Neuroprotective Agents)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - *Alzheimer Disease/drug therapy/metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognitive Dysfunction/metabolism
MH  - Disease Models, Animal
MH  - Exenatide/*pharmacology
MH  - Female
MH  - Glucagon-Like Peptide 1/metabolism
MH  - Glucose Tolerance Test/methods
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice
MH  - Neuroimmunomodulation/drug effects
MH  - *Neuronal Plasticity/drug effects/physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Aging
OT  - BDNF
OT  - T2DM
OT  - dementia
OT  - diabetes
OT  - exendin-4
OT  - insulin
OT  - insulin resistance
OT  - neurotrophic factors
EDAT- 2019/07/01 06:00
MHDA- 2020/10/10 06:00
CRDT- 2019/07/01 06:00
PHST- 2019/07/01 06:00 [pubmed]
PHST- 2020/10/10 06:00 [medline]
PHST- 2019/07/01 06:00 [entrez]
AID - JAD190237 [pii]
AID - 10.3233/JAD-190237 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2019;70(3):793-810. doi: 10.3233/JAD-190237.