Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress.
We report that 9 d of uncontrolled experimental diabetes induced by streptozotocin (STZ) in rats is an endogenous chronic stressor that produces retraction and simplification of apical dendrites of hippocampal CA3 pyramidal neurons, an effect also observed in nondiabetic rats after 21 d of repeated restraint stress or chronic corticosterone (Cort) treatment. Diabetes also induces morphological changes in the presynaptic mossy fiber terminals (MFT) that form excitatory synaptic contacts with the proximal CA3 apical dendrites. One effect, synaptic vesicle depletion, occurs in diabetes as well as after repeated stress and Cort treatment. However, diabetes produced other MFT structural changes that differ qualitatively and quantitatively from other treatments. Furthermore, whereas 7 d of repeated stress was insufficient to produce dendritic or synaptic remodeling in nondiabetic rats, it potentiated both dendritic atrophy and MFT synaptic vesicle depletion in STZ rats. These changes occurred in concert with adrenal hypertrophy and elevated basal Cort release as well as hypersensitivity and defective shutoff of Cort secretion after stress. Thus, as an endogenous stressor, STZ diabetes not only accelerates the effects of exogenous stress to alter hippocampal morphology; it also produces structural changes that overlap only partially with those produced by stress and Cort in the nondiabetic state.
Magariños
A M
AM
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. magaria@rockvax.rockefeller.edu
McEwen
B S
BS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D003345:Corticosterone / Q000008:administration & dosage* / Q000502:physiology; D003712:Dendrites / Q000473:pathology* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D013312:Stress, Physiological / Q000473:pathology* / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology* / Q000502:physiology
D000900:Anti-Bacterial Agents; D013311:Streptozocin; D003345:Corticosterone