Protective effects of testosterone on WR motoneuron degeneration.

GONZALEZ DENISELLE MC; GUENNOUN R; DI GIORGIO NP; LARA A; DE NICOLA A; LUX-LANTOS V; MEYER M; GARGIULO MONACHELLI G; LIMA A; GARAY L

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Wobbler(WR) mouse is an animal model for human amyotrophiclateral sclerosis(ALS). We have shown neuroprotective effects ofprogesteronein WRs. Here, we studied if testosterone (T) treatmentwasneuroprotective. Since low T levels were shown in WR?sserum andspinal cord from WRs, two month-old male WRs weretreatedwith T (silastic tube s.c. implant with T crystals) for 60 days.We examinedclinical motoneuron disabilities, T serum levels andendocrineparameters: hypophysis, testicles, seminal vesicles andadrenalglands weight were measured. We also evaluated in cervicalspinalcord: 1) the number of microglial Iba1+ cells in ventralhorn byimmunofluorescence, 2) expression of toll-like receptor 4(TLR4) andtransforming growth factor b (TGFb) mRNAs, and 3)steroidogenicacute regulatory protein (StAR) and the translocatorprotein(TSPO) mRNAs by qPCR. WRs had higher testicle andadrenal(p<0.01) mass and lower seminal vesicles (p<0.01 vs controls).T treatmentyielded a three-fold increase in its serum levels(p<0.05vs WR). WR?s hypophysis, a parameter sensitive to aromatizableandrogens,and adrenal gland weights were not modifiedby T, whileT decreased testicles (p<0.01) and increased seminalvesicles(p<0.01). Except for TGFb mRNA levels, WR?s cervical spinalcord showedhigh levels of: 1) Iba1+ cells (p<0.01), 2) TLR4mRNA(p<0.05), 3) StAR and TSPO mRNAs (p<0.001). T treatmentsignificantlyreduced Iba1+ cells (p<0.01), TRL4 and StAR mRNAs(p<0.05),although TSPO was not affected. However, high levels ofTGFb mRNAwas found in WR+T (p<0.05 vs WR). Clinically, T alsodelayedclinical abnormalities in WRs (p<0.01 vs WR). In summary,pharmacologicaladministration of T to WRs reduced inflammatoryandsteroidogenic mitochondrial parameters, while delayed motordisabilityand increased seminal vesicles trophism. To conclude,protectiveeffect of T may involve the modulation of inflammatoryandsteroidogenic factors in WR´s motoneuron degeneration.Keywords:Testosterone; Wobbler; neuroprotection; amyotrophiclateralsclerosis.