Protective effects of testosterone on WR motoneuron degeneration

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

Congreso; LXII Reunión de la Sociedad Argentina de Investigación Clínica; 2017

Wobbler (WR) mouseis an animal model for human amyotrophic lateral sclerosis (ALS). We have shown neuroprotective effects of progesterone inWRs. Here, we studied if testosterone (T) treatment was neuroprotective.Since low T levels were shown in WR?s serum and spinal cord from WRs, twomonth-old male WRs were treated with T (silastictube s.c. implant with T crystals) for 60 days. We examined clinical motoneurondisabilities, T serum levels and endocrine parameters: hypophysis, testicles,seminal vesicles and adrenal glands weight were measured. We also evaluated incervical spinal cord: 1) the number of microglial Iba1+ cells in ventral hornby immunofluorescence, 2) expression of toll-like receptor 4(TLR4) and transforming growth factor b (TGFb) mRNAs, and3) steroidogenic acute regulatory protein (StAR) and the translocator protein (TSPO)mRNAs by qPCR. WRs had higher testicle and adrenal (p<0.01) mass and lower seminalvesicles (p<0.01 vs controls). T treatment yielded a three-fold increase inits serum levels (p<0.05 vs WR). WR?s hypophysis, a parameter sensitive toaromatizable androgens, and adrenal gland weights were not modified by T, whileT decreased testicles (p<0.01) and increased seminal vesicles (p<0.01). Exceptfor TGFb mRNA levels, WR?s cervical spinalcord showed high levels of: 1) Iba1+ cells (p<0.01), 2) TLR4 mRNA (p<0.05),3) StAR and TSPO mRNAs (p<0.001). T treatment significantly reduced Iba1+cells (p<0.01), TRL4 and StAR mRNAs (p<0.05), although TSPO was notaffected. However, high levels of TGFb mRNAwas found in WR+T (p<0.05 vs WR). Clinically, T also delayed clinicalabnormalities in WRs (p<0.01 vs WR).In summary, pharmacological administration of T to WRs reducedinflammatory and steroidogenic mitochondrial parameters, while delayed motor disabilityand increased seminal vesicles trophism. To conclude, protective effect of T may involve the modulation of inflammatory and steroidogenic factors in WR?smotoneuron degeneration.