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

Alexis Michelle Stranahan, Thiruma V. Arumugam, Roy G. Cutler, Kim Lee, Josephine M. Egan, Mark P. Mattson

Research output: Contribution to journalArticle

401 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)309-317
Number of pages9
JournalNature Neuroscience
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2008

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Corticosterone
Glucocorticoids
Neuronal Plasticity
Neurogenesis
Neurons
Insulin
Perforant Pathway
Neurosecretory Systems
Streptozocin
Hyperglycemia
Insulin Resistance
Hippocampus
Obesity
Steroids
Learning
Brain
Cognitive Dysfunction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. / Stranahan, Alexis Michelle; Arumugam, Thiruma V.; Cutler, Roy G.; Lee, Kim; Egan, Josephine M.; Mattson, Mark P.

In: Nature Neuroscience, Vol. 11, No. 3, 01.03.2008, p. 309-317.

Research output: Contribution to journalArticle

Stranahan, Alexis Michelle ; Arumugam, Thiruma V. ; Cutler, Roy G. ; Lee, Kim ; Egan, Josephine M. ; Mattson, Mark P. / Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. In: Nature Neuroscience. 2008 ; Vol. 11, No. 3. pp. 309-317.
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