Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons.
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.
Stranahan
Alexis M
AM
Psychology Department, Princeton University, Green Hall Washington Road, Princeton, New Jersey 08544, USA.
Arumugam
Thiruma V
TV
Cutler
Roy G
RG
Lee
Kim
K
Egan
Josephine M
JM
Mattson
Mark P
MP
D000818:Animals; D001928:Brain Diseases, Metabolic / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism*; D006624:Hippocampus / Q000503:physiopathology*; D007328:Insulin / Q000172:deficiency; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D019580:Perforant Pathway / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D007328:Insulin; D003345:Corticosterone