TY - JOUR
T1 - Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons
AU - Stranahan, Alexis M.
AU - Arumugam, Thiruma V.
AU - Cutler, Roy G.
AU - Lee, Kim
AU - Egan, Josephine M.
AU - Mattson, Mark P.
N1 - Funding Information:
This research was supported by US National Institutes of Health National Research Service Award Predoctoral fellowship F31AG024690-03 to A.M.S. through Princeton University, and by the Intramural Research Program of the US National Institute on Aging. We thank D.L. Longo for suggestions and T. Lamb, O. Carlson, J.S. Villareal and R. Telljohann for technical assistance. We are also grateful to E. Gould and H. van Praag for comments on the manuscript.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
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U2 - 10.1038/nn2055
DO - 10.1038/nn2055
M3 - Article
C2 - 18278039
AN - SCOPUS:39749137437
SN - 1097-6256
VL - 11
SP - 309
EP - 317
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 3
ER -