Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance

Ewan C. McNay, Cecilia T. Ong, Rory J. McCrimmon, James Cresswell, Jonathan S. Bogan, Robert S. Sherwin

    Research output: Contribution to journalArticlepeer-review

    251 Citations (Scopus)

    Abstract

    Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes. Published by Elsevier Inc.

    Original languageEnglish
    Pages (from-to)546-553
    Number of pages8
    JournalNeurobiology of Learning and Memory
    Volume93
    Issue number4
    DOIs
    Publication statusPublished - May 2010

    Keywords

    • Glucose
    • Insulin
    • Spatial memory
    • Hippocampus
    • Diabetes
    • GLUCOSE-TRANSPORTER EXPRESSION
    • PASSIVE-AVOIDANCE TASK
    • OBESE ZUCKER RATS
    • ALZHEIMERS-DISEASE
    • AGED RATS
    • RECURRENT HYPOGLYCEMIA
    • SYNAPTIC PLASTICITY
    • SIGNAL-TRANSDUCTION
    • INTRANASAL INSULIN
    • DIABETES-MELLITUS

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