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 strepto zotocin (STZ) in rats is an endogenous chronic stressor that produces retra ction and simplification of apical dendrites of hippocampal CA3 pyramidal n eurons, 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 dendr ites. 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 o ther treatments. Furthermore, whereas 7 d of repeated stress was insufficie nt to produce dendritic or synaptic remodeling in nondiabetic rats, it pote ntiated both dendritic atrophy and MFT synaptic vesicle depletion in STZ ra ts. These changes occurred in concert with adrenal hypertrophy and elevated basal Cort release as well as hypersensitivity and defective shutoff of Co rt secretion after stress. Thus, as an endogenous stressor. STZ diabetes no t only accelerates the effects of exogenous stress to alter hippocampal mor phology; it also produces structural changes that overlap only partially wi th those produced by stress and Cort in the nondiabetic state.