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

被引:491
作者
Stranahan, Alexis M. [1 ,3 ]
Arumugam, Thiruma V. [1 ]
Cutler, Roy G. [1 ]
Lee, Kim [1 ]
Egan, Josephine M. [2 ]
Mattson, Mark P. [1 ]
机构
[1] NIA, Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, Baltimore, MD 21224 USA
[2] NIA, Intramural Res Program, Diabet Sect, Lab Child Invest, Baltimore, MD 21224 USA
[3] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA
关键词
D O I
10.1038/nn2055
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:309 / 317
页数:9
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