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Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet

Gault, V.A., Porter, W.D., Flatt, P.R., Holscher, C.
International journal of obesity 2010 v.34 no.8 pp. 1341–1344
memory, synapse, high fat diet, drug therapy, drugs, energy metabolism, disease control, mice, noninsulin-dependent diabetes mellitus, animal models, obesity, electrophysiology, cognition, biochemical mechanisms, synaptic transmission, hippocampus, glucagon-like peptides
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.