Mineralocorticoid receptor activation restores medial perforant path LTP in diabetic rats

Authors

  • Alexis M. Stranahan,

    1. Psychology Department, Princeton University, Princeton, New Jersey
    2. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland
    Current affiliation:
    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore
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  • Thiruma V. Arumugam,

    1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland
    Current affiliation:
    1. School of Biomedical Sciences, The University of Queensland, Street Lucia, Australia
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  • Kim Lee,

    1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland
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  • Mark P. Mattson

    Corresponding author
    1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland
    • Laboratory of Neurosciences, Biomedical Research Center, 05C214, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21,224-6825, USA
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Abstract

In the hippocampus, glucocorticoids bind to two types of receptors: the mineralocorticoid receptor, which binds corticosterone with high affinity and is tonically occupied; and the glucocorticoid receptor, which is occupied during stress and at certain phases in the circadian cycle. Diabetes mellitus increases levels of glucocorticoids in both humans and animal models. To explore the contributions of hippocampal corticosteroid receptors to the diabetes-induced suppression of neuroplasticity, we manipulated these receptors in hippocampal slices from streptozocin-diabetic rats, a model of Type 1 diabetes mellitus. STZ-diabetes reduced long-term potentiation (LTP) at medial perforant path synapses in the dentate gyrus, and induced a bias in favor of long-term depression following intermediate stimulation frequencies. Bath application of the mineralocorticoid receptor agonist aldosterone restored LTP in slices from diabetic animals. These results suggest additional mechanisms for diabetes-induced functional alterations and support a restorative role for dentate gyrus mineralocorticoid receptors. Synapse 64:528–532, 2010. © 2010 Wiley-Liss, Inc.

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