Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels.
Diabetes and normal aging are both characterized by increases in levels of glucocorticoids. Because long-term exposure to elevated glucocorticoids can be detrimental to hippocampal function, we evaluated the performance of young diabetic rats in the 14-unit T-maze, a task that is sensitive to hippocampal deficits. To assess the contribution of diabetes-induced elevations in corticosterone levels, we examined maze learning in diabetic rats that had levels of corticosterone 'clamped' through adrenalectomy and low-dose corticosterone replacement. For comparison, we also tested a separate group of young and aged rats in the maze. Adrenally intact diabetic rats learned poorly in the 14-unit T-maze. Preventing the increases in corticosterone levels that accompanies the onset of experimental diabetes also prevented deficits in complex maze learning. The pattern of errors made by adrenally intact diabetic rats was similar to the pattern of errors made by aged rats, suggesting that the cognitive profiles of diabetic and aged rats share common features.
Stranahan
Alexis M
AM
Cellular and Molecular Neuroscience Section, Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
Lee
Kim
K
Pistell
Paul J
PJ
Nelson
Christopher M
CM
Readal
Nathaniel
N
Miller
Marshall G
MG
Spangler
Edward L
EL
Ingram
Donald K
DK
Mattson
Mark P
MP
D000315:Adrenalectomy; D000375:Aging / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D003345:Corticosterone / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004597:Electroshock; D004924:Escape Reaction / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000502:physiology
D003345:Corticosterone