Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet.
High-calorie diet has been shown to impair learning ability and hippocampal synaptic plasticity in rodents. This study examined effects of daily treatment with the glucagon-like peptide-1 mimetic, exendin-4, on cognitive function and hippocampal synaptic plasticity in a model of diet-induced obesity, which exhibits compromised cognitive performance. Mice fed a high-fat diet were treated with exendin-4 (25 nmol kg(-1) bodyweight; twice daily) or saline vehicle (0.9% (w/v) NaCl) over 21 days. In addition to improving metabolic control, exendin-4-treated mice exhibited a marked increase in recognition index highlighting improved learning and memory. High-fat diet resulted in the elimination of in vivo electrophysiological long-term potentiation, which was rescued following exendin-4 treatment. This study shows that exendin-4 therapy improves cognitive function and ameliorates impaired hippocampal synaptic plasticity in dietary-induced obesity.
Gault
V A
VA
The SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK. va.gault@ulster.ac.uk
Porter
W D
WD
Flatt
P R
PR
Hölscher
C
C
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage; D000077270:Exenatide; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
D004041:Dietary Fats; D010455:Peptides; D014688:Venoms; D000077270:Exenatide