Article abstract
Nature Neuroscience 11, 309 - 317 (2008)
Published online: 17 February 2008 | doi:10.1038/nn2055
Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons
Alexis M Stranahan1,2, Thiruma V Arumugam2,4, Roy G Cutler2, Kim Lee2, Josephine M Egan3 & Mark P Mattson2
Abstract
Many organ systems are adversely affected by diabetes, including the brain, which undergoes changes that may increase the risk of cognitive decline. Although diabetes influences the hypothalamic-pituitary-adrenal axis, the role of this neuroendocrine system in diabetes-induced cognitive dysfunction remains unexplored. Here we demonstrate that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects. Rats treated with streptozocin have reduced insulin and show hyperglycemia, increased corticosterone, and impairments in hippocampal neurogenesis, synaptic plasticity and learning. Similar deficits are observed in db/db mice, which are characterized by insulin resistance, elevated corticosterone and obesity. Changes in hippocampal plasticity and function in both models are reversed when normal physiological levels of corticosterone are maintained, suggesting that cognitive impairment in diabetes may result from glucocorticoid-mediated deficits in neurogenesis and synaptic plasticity.
- Psychology Department, Princeton University, Green Hall Washington Road, Princeton, New Jersey 08544, USA.
- Laboratory of Neurosciences, Cellular and Molecular Neurosciences Section, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
- Present address: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79430, USA.
Correspondence to: Mark P Mattson2 e-mail: mattsonm@grc.nia.nih.gov
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