Metabolism and effects of testosterone in the spinal cord from Wobbler-ALS mice after treatment with exogenous testosterone

ESPERANTE IVAN; MEYER M; LARA AGUSTINA; LIERE P; LIMA A; ROIG P; GUENNOUN R; DE NICOLA A. F.; GONZALEZ DENISELLE MC

Congreso; LXV Reunión Científica de la Sociedad Argentina de Investigacion Clinica,; 2020

Amyotrophic lateral sclerosis (ALS) patients present motoneuron degeneration leading to muscle atrophy, dysphagia and dysarthria. The Wobbler (WR) mouse, an ALS animal model, shows a selective loss of motoneurons, astrocytosis and microgliosis in cervical spinal cord. The incidence of ALS is greater in men; however it increases in women after menopause, suggesting a role of sex steroids in ALS. Testosterone is a complex steroid that exerts its effects directly via androgen (AR) and indirectly via estrogen receptors (ER) after aromatization into estradiol. Its reduced-metabolite 5-dihydrotestosterone acts via AR. This study analyzed the metabolism of testosterone in the spinal cord and studied testosterone effects on myelin basic protein (MBP) and rotarod performance in male symptomatic WRs. Controls or WRs received empty or testosterone-filled silastic tubes for 2 months. The cervical spinal cord from testosterone-treated WRs showed: 1) similar androgen levels to untreated control, and 2) increased levels of testosterone (p