EXPRESSION OF BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) IS DIMINISHED IN THE DENTATE GYRUS OF STREPTOZOTOCIN (STZ) DIABETIC MICE: REVERSION BY FLUOXETINE TREATMENT

BEAUQUIS, J; GONZALEZ-DENISELLE-MC; GARAY, L; PIETRANERA, L; GONZALEZ, S; ROIG, P; HOMO-DELARCHE, F; DE NICOLA, AF; SARAVIA, F

Buenos Aires

Congreso; Sociedad Argentina de Biología; 2005

SAB

Type 1 diabetes correlates with several disturbances of the CNS in humans and in experimental animal models. The hippocampus is one of the most vulnerable structures. Previously we reported that STZ diabetic mice showed less dentate gyrus neurogenesis than controls and that a 10-day treatment with fluoxetine (FXT, 10 mg/kg BW) reversed this situation. In the present work our objective was to determine BDNF mRNA in the hippocampus of diabetic mice and the effect of FXT on this factor, which is closely related to neuronal plasticity and functionality. Male adult C57BL/6 mice were given STZ (195 mg/kg BW) and, after 10 days, FXT or vehicle was given for 10 more days. We performed in situ hybridization (ISH) with a S35 labeled probe to measure BDNF mRNA and quantified the optical density of the dentate gyrus in the autoradiographic films. In diabetic mice, BDNF mRNA level was significantly lower than in controls (CTL:129±4.3, STZ:110±2.75, p<0.01) and  FXT reversed completely the effect of diabetes, leading to levels similar than in controls (STZ+FXT:125.4±3.0, p<0.05 vs. STZ; CTL+FXT:123.4±2.0). In another group of mice we performed non isotopic ISH for BDNF mRNA and BrdU detection of proliferating cells in the dentate gyrus and we found that recently divided cells are positive for BDNF mRNA. These results suggest that in the diabetic brain the expression of trophic factors is altered and that BDNF plays and a role in the action of FXT in the neurogenic process and over adult granule cells.