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Int J Obes (Lond). 2010 Aug;34(8):1341-4. doi: 10.1038/ijo.2010.59. Epub 2010 Mar 30.

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

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The SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.


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.

[Indexed for MEDLINE]

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