Mineralocorticoid receptor activation restores medial perforant path LTP in diabetic rats

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.