Neuroendocrinology and Neuroimmunology
Author: Ivan Jose Esperante | Email: esperanteibyme@gmail.com
Ivan J. Esperante1°, Maria Meyer1°, Carolina Banzan1°, Philip Liere4°, Analia Lima1°, Paulina Roig1°, Rachida Guennoun4°, Alejandro F De Nicola1°3°, Maria Claudia Gonzalez Deniselle1°2°
1° Instituto de Biología y Medicina Experimental (IBYME-CONICET)
2° Dto de Ciencias Fisiológicas, Facultad de Medicina, UBA
3° Dto de Bioquímica Humana, Facultad de Medicina, UBA
4° U1195 INSERM and University Paris Sud: “Neuroprotective, neuroregenerative and remyelinating small molecules”
The Wobbler mouse (WR), a recognized model of ALS, shows a selective loss of motoneurons associated to astrocytosis and microgliosis in cervical spinal cord (CSC) and brainstem. We have demonstrated neuroprotective effects of testosterone (T) and modulation of neurosteroidogenic enzymes in the WR’s CSC. Here, we investigated T and flutamide (F) effects on superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX1) mRNAs and on steroid levels in male WR’s CSC. T was implanted in silastic tubes (2 months). F was given in pellets (20mg) starting 1 week before T. Four groups were prepared: a) WR, (b) control+empty silastic tubes, c) WR+T (silastic tubes+T) and d) WR+T+F. T but not T+F increased seminal vesicles and biceps weight (p<0.05 vs WR). In WR+T, we showed: 1) high expression of SOD1 (p<0.05), GPX1 (p<0.01), and SIRT3 mRNAs (p<0.001) vs. WRs and WR+T+F; 2) high levels of T, 5α-dihydrotestosterone (5α-DHT), and 3β-androstanediol (p<0.01 vs. WR and WR+T+F); 3) high levels of 3a-androstanediol, a GABA A agonist, vs. WRs (p<0.05) but not vs. WR+T+F; 4) a positive association between grip strength and T or 3β-androstanediol (p<0.05) and 5) a negative association between paw atrophy and 5α-DHT levels (p<0.01 vs WR, NS vs WR+T+F). We suggest that the androgen receptor may be involved in T protective mechanisms against motoneuron degeneration and propose considering androgen derivatives as potential prognostic biomarkers for this condition.