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

Author:
Gault, V.A., Porter, W.D., Flatt, P.R., Holscher, C.
Source:
International journal of obesity 2010 v.34 no.8 pp. 1341–1344
ISSN:
0307-0565
Subject:
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
Abstract:
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.
Agid:
792191