Protective effects of testosterone on WR motoneuron degeneration.

GARGIULO MONACHELLI G; DI GIORGIO N; LARA AGUSTINA; GONZALEZ DENISELLE MC; LUX-LANTOS V; MEYER M; DE NICOLA A. F.; GARAY L

Congreso; Reunión Anual Conjunta de las Sociedades de Biociencias; 2017

Wobbler (WR) mouse is an animal model for human amyotrophiclateral sclerosis (ALS). We have shown neuroprotective effects ofprogesterone in WRs. Here, we studied if testosterone (T) treatmentwas neuroprotective. Since low T levels were shown in WR?sserum and spinal cord from WRs, two month-old male WRs weretreated with T (silastic tube s.c. implant with T crystals) for 60 days.We examined clinical motoneuron disabilities, T serum levels andendocrine parameters: hypophysis, testicles, seminal vesicles and adrenal glands weight were measured. We also evaluated in cervicalspinal cord: 1) the number of microglial Iba1+ cells in ventralhorn by immunofluorescence, 2) expression of toll-like receptor 4(TLR4) and transforming growth factor b (TGFb) mRNAs, and 3)steroidogenic acute 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 treatment yielded a three-fold increase in its serum levels(p<0.05 vs WR). WR?s hypophysis, a parameter sensitive to aromatizableandrogens, and adrenal gland weights were not modifiedby T, while T decreased testicles (p<0.01) and increased seminalvesicles (p<0.01). Except for TGFb mRNA levels, WR?s cervical spinalcord showed high levels of: 1) Iba1+ cells (p<0.01), 2) TLR4mRNA (p<0.05), 3) StAR and TSPO mRNAs (p<0.001). T treatmentsignificantly reduced Iba1+ cells (p<0.01), TRL4 and StAR mRNAs(p<0.05), although TSPO was not affected. However, high levels ofTGFb mRNA was found in WR+T (p<0.05 vs WR). Clinically, T alsodelayed clinical abnormalities in WRs (p<0.01 vs WR). In summary,pharmacological administration of T to WRs reduced inflammatoryand steroidogenic mitochondrial parameters, while delayed motordisability and increased seminal vesicles trophism. To conclude,protective effect of T may involve the modulation of inflammatoryand steroidogenic factors in WR?s motoneuron degeneration.