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PMID: 18278039 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

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

Nature neuroscience ·Vol. 11 ·No. 3 ·2008-03-00 ·Pages 309-17

Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP

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.

MeSH Terms
Animals Brain Diseases, Metabolic/etiology,metabolism,physiopathology Cell Differentiation/genetics Cell Proliferation Cognition Disorders/etiology,metabolism,physiopathology Corticosterone/blood Diabetes Mellitus, Experimental/complications,metabolism,physiopathology Glucocorticoids/blood,metabolism Hippocampus/physiopathology Insulin/deficiency Insulin Resistance/genetics Male Memory Disorders/etiology,metabolism,physiopathology Mice Mice, Inbred C57BL Mice, Transgenic Neuronal Plasticity Neurons/metabolism Perforant Pathway/metabolism,physiopathology Rats Rats, Sprague-Dawley
Chemicals
Glucocorticoids Insulin Corticosterone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Stranahan Alexis M
Psychology Department, Princeton University, Green Hall Washington Road, Princeton, New Jersey 08544, USA.
Arumugam Thiruma V
Cutler Roy G
Lee Kim
Egan Josephine M
Mattson Mark P
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1097-6256
DOI
10.1038/nn2055
Published
2008-03-00
Epub
2008-00-17
Pages
309-17
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2927988
Subset
IM
Grants
NIA NIH HHS · F31 AG024690-03 · United States
Intramural NIH HHS · Z01 AG000314-07 · United States
NIA NIH HHS · F31AG024690-03 · United States
NIA NIH HHS · F31 AG024690-04 · United States
NIA NIH HHS · F31 AG024690 · United States
Intramural NIH HHS · Z01 AG000313-07 · United States
Intramural NIH HHS · Z01 AG000312-07 · United States
NIA NIH HHS · F31 AG024690-02 · United States
NIA NIH HHS · F31 AG024690-01 · United States
External Links
PubMed source DOI: 10.1038/nn2055 PMC Full Text View journal details
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