Progesterone increases neuronal BDNF expression in Wobbler mice, a model of spinal cord motoneuron disease

GONZÁLEZ DENISELLE, M. C.; GONZALEZ, S.L; GARAY L; LABOMBARDA F; GUENNOUN R; SCHUMACHER M; DE NICOLA AF

Washington, DC, Estados Unidos

Congreso; 35th Annual meeting of the Society for Neuroscience; 2005

Society for Neuroscience

Progesterone (PROG) provides neuroprotection in spinal cord neurodegeneration and injury. These effects may be due to regulation of myelination in glia and to direct actions on neuronal function. Recent studies point to neurotrophins as mediators of hormone action. Here, we show that BDNF mRNA expression analyzed by in situ hydridization (ISH) was increased by PROG treatment in ventral horn from mice with spinal cord neurodegeneration (Wobblers). One month old clinically afflicted Wobblers were treated with a s.c. pellet of 20 mg PROG, and studied 60 days afterwards. Computerized image analysis of mRNA expression showed that the number of grains per unit area decreased by 70% in untreated Wobblers (9. 0 1.31 vs control 30.0 2, p<0.01) and by 45% in cells >600 um2 (12.16 1.51 vs. control 22.36 0.72, p<0.01). In PROG-treated Wobblers, grain density increased 2.5-fold in neurons <600 um2 (22.15 2.0 , p<0.05 vs untreated Wobblers) and 1.5-fold in neurons >600 um2 (17,27 1.96, p<0.05 vs. untreated group). We also studied the activity of choline acetyltransferase (ChAT) in nerve terminals, considering its close relationship to BDNF. Whereas ChAT activity was reduced by 55.3% in untreated Wobblers, PROG induced a slight but significant increment (p<0.05). Finally, we investigated PROG effects on motoneuron morphology, which showed cytoplasmic vacuolation in untreated Wobblers. Although few motoneurons in PROG-treated Wobblers still presented an attenuated vacuolation, PROG treatment reduced 6-fold the percentage of vacuolated cells(p<0.05). We suggest that PROG enhancement of endogenous BDNF could provide a trophic environment and might be part of the PROG activated-pathways to provide neuroprotection in spinal cord neurodegeneration.