Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats.
Overall dietary energy intake, particularly the consumption of simple sugars such as fructose, has been increasing steadily in Western societies, but the effects of such diets on the brain are poorly understood. Here, we used functional and structural assays to characterize the effects of excessive caloric intake on the hippocampus, a brain region important for learning and memory. Rats fed with a high-fat, high-glucose diet supplemented with high-fructose corn syrup showed alterations in energy and lipid metabolism similar to clinical diabetes, with elevated fasting glucose and increased cholesterol and triglycerides. Rats maintained on this diet for 8 months exhibited impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation at Schaffer collateral--CA1 synapses. These changes occurred concurrently with reductions in levels of brain-derived neurotrophic factor in the hippocampus. We conclude that a high-calorie diet reduces hippocampal synaptic plasticity and impairs cognitive function, possibly through BDNF-mediated effects on dendritic spines.
Stranahan
Alexis M
AM
Cellular and Molecular Neurosciences Section, Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, USA.
Norman
Eric D
ED
Lee
Kim
K
Cutler
Roy G
RG
Telljohann
Richard S
RS
Egan
Josephine M
JM
Mattson
Mark P
MP
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D004040:Dietary Carbohydrates; D004041:Dietary Fats