Fluoxetine treatment reverses several hippocampal alterations in streptozotocin diabetic mice.

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

Melbourne, Australia

Congreso; VII World Congress of Neuroscience, International Brain Research Organization; 2007

International Brain Research Organization

Diabetes mellitus correlates with a brain encephalopathy sharing characteristics with depression. Increased risk of dementia, stroke and depression, are common findings in diabetics. Previously, we reported that fluoxetine treatment was able of increasing neurogenesis in the dentate gyrus (DG) of streptozotocin diabetic mice, a model of type 1 diabetes. Here we report that fluoxetine (FXT) treatment increased the survival of new neurons in the DG of diabetic animals using the bromodesoxyuridine (BrdU, a single dose of 250 mg/kg 10 days before sacrifice) technique (controls, CTL:718.7±99.1, CTL+FXT:604.6±37.4, diabetics, DIAB:432.3±73.5 p<0.05 vs CTL, DIAB+FXT:1342±272.9 BrdU+ cells/DG p<0.005 vs DIAB). Co-labeling with specific markers confirmed neural phenotype. We studied pyknotic cells as indicator of cell death and found an increase in diabetic mice and reversion with fluoxetine treatment (CTL:65.6±5.1, CTL+FXT:56±18.9, DIAB:152±16.9 p<0.01 vs CTL, DIAB+FXT:86.1±10.62 cells/DG p<0.01 vs DIAB). BDNF-linked to neurogenesis regulation and survival- was studied by in situ hybridization. We found low content of BDNF mRNA in diabetic animals and a significant increase in fluoxetine treated diabetics (CTL:129±4.3, DIAB:110.1±2.7, p<0.01, DIAB+FXT: 125.4±3, p<0.05 vs DIAB; optical density in DG). Although the function of NG2+ cells is controversial, the proteoglycan is associated with axonal growth inhibition and neurodegeneration. The number of NG2+ cells in the hilus increased in diabetic mice; fluoxetine treatment decreased it to control level. This work contributes to further understanding of the impact of diabetes on the brain reporting decreased cell survival, increased cell loss and suffering, declined neurotrophic factor expression and augmented glial reactivity. Fluoxetine was able to reverse these changes, suggesting a protective role in the CNS.