Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons

Stranahan, Alexis M., Arumugam, Thiruman V., Cutler, Roy G., Lee, Kim, Egan, Josephine M. and Mattson, Mark P. (2008) Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nature Neuroscience, 11 3: 309-317. doi:10.1038/nn2055


Author Stranahan, Alexis M.
Arumugam, Thiruman V.
Cutler, Roy G.
Lee, Kim
Egan, Josephine M.
Mattson, Mark P.
Title Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons
Journal name Nature Neuroscience   Check publisher's open access policy
ISSN 1097-6256
1546-1726
Publication date 2008-03
Sub-type Article (original research)
DOI 10.1038/nn2055
Volume 11
Issue 3
Start page 309
End page 317
Total pages 9
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 12:22:17 EST