Neuronal plasticity and antidepressants in the diabetic brain.
The hippocampus, a limbic structure linked to higher brain functions, appears vulnerable in diabetic subjects that have a higher risk of stroke, dementia, and cognitive decline. The dentate gyrus (DG) of the hippocampus is one of the limited neurogenic brain areas during adulthood; neurons born in the DG are involved in some types of learning and memory processes. We found a decrease in the ability for proliferation and neuronal differentiation of newborn cells, measured by bromodeoxyuridine incorporation in the DG, from streptozotocin-induced diabetic mice. The hilar region, formed by mature neurons presenting higher sensitivity to brain damage, showed a reduced neuronal density in diabetic mice with respect to vehicle-treated mice. Interestingly, in a spontaneous model of type 1 diabetes, we corroborated a decrease in the rate of neurogenesis in the nonobese diabetic mice compared to control strains, and this reduction was also found during the prediabetic stage. The antidepressant fluoxetine administered over a period of 10 days to diabetic mice was effective in preventing changes in proliferation and differentiation of new neurons. Confocal microscope studies, including using neuronal and glial markers, suggested that differentiation toward a neuronal phenotype was decreased in diabetic animals and was reversed by the antidepressant treatment. In addition, the loss of hilar neurons was avoided by fluoxetine treatment. Several reports have demonstrated that high susceptibility to stress and elevated corticosterone levels are detrimental to neurogenesis and contribute to neuronal loss. These features are common in some types of depression, diabetes, and aging processes, suggesting they participate in the reported hippocampal abnormalities present in these conditions.
Beauquis
Juan
J
Neuroendocrine Biochemistry, Institute of Biology and Experimental Medicine, National Research Council, Buenos Aires, Argentina.
Roig
Paulina
P
De Nicola
Alejandro F
AF
Saravia
Flavia
F
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001927:Brain Diseases / Q000150:complications; D018891:Dentate Gyrus / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*
D000928:Antidepressive Agents