Fluoxetine treatment reverses several hippocampal alterations in streptozotocin diabetic mice.

BEAUQUIS J; ROIG P; GARAY L; LABOMBARDA F; GONZÁLEZ S; HOMO-DELARCHE F; DE NICOLA AF; SARAVIA F

Madrid, España.

Congreso; 2nd Iberoamerican Congress on Neuroimmunomodulation.; 2007

International Society for Neuroimmunomodulation

Diabetes mellitus is associated with brain alterations that constitute the diabetic encephalopathy and shares many characteristics with depression. We have reported that fluoxetine -an antidepressant, serotonin reuptake inhibitor- treatment was able of correcting the poor hippocampal proliferation rate in the dentate gyrus of streptozotocin diabetic mice, a pharmacological model of type 1 diabetes. Here, we report that fluoxetine treatment increased the survival of new neurons in diabetic animals using the bromodeoxyuridine labeling technique. Neural phenotype was confirmed by co-labeling with specific markers. The number of pyknotic cells showed a marked increase in diabetic mice. Content of BDNFmRNA -linked to neurogenesis and cell survival- by in situ hybridization, was low in the dentate gyrus of diabetic animals and increased by fluoxetine. Although the function and regulation of NG2+ cells is controversial, the proteoglycan NG2 is associated to axonal growth inhibition and neurodegeneration. The number of NG2+ cells in the hilus of diabetic mice increased compared with controls and antidepressant decreased it. This work displays new evidence of hippocampal alterations in diabetes, a metabolic disease, reporting decreased cell survival, increased cell loss and suffering and glial reactivity, and declined neurotrophic factor expression. Fluoxetine reversed these changes, suggesting a protective role of the antidepressant in the brain.