Muscle trophism after testosterone treatment in the Wobbler mouse, a spontaneous model for amyotrophic lateral sclerosis (ALS)

MEYER M; LIMA A; DE NICOLA AF; LARA A; GARAY L; GUENNOUN R; ESPERANTE I; DE NICOLA F; ROIG P; GONZÁLEZ DENISELLE MC

Mar del Plata

Congreso; Reunión de la Sociedad Argentina de Investigación Clínica; 2019

Patients suffering amyotrophiclateral sclerosis (ALS) present muscle atrophy in upper and lower limbs anddifficulties in swallowing and dysarthria in association to motoneurondegeneration. Wobblers mice (WR) are animal models of ALS showing selectiveloss of motoneurons, astrocytosis and microgliosis in the ventral horn of thecervical spinal cord. The incidence of ALS is greater in men than in women,however it increases after menopause. Previously we demonstrated that testosteronetreatment to WRs reduced astrocytosis and increased glutamine synthetase immunoreactivity,an enzyme necessary formaintaining glutamate concentration in synaptic cleft. Now, we investigated the effect of testosterone treatment onmyelination and muscle trophism. Treatment consisted of 10mm silastic tubes containing crystalline testosterone s.c. for 2 months to male symptomatic WRs. Testosteroneserum levels and seminal vesicles weight were higher in WRs+testosterone vs WRs(p<0.05). Luxol fast blue (LFB) stain was used to identify myelin andwe quantified the percentageof area stained over a threshold in white matter of the cervical cord. In WR mice treated with testosterone, the percentage of stainedarea for LFB in the ventrolateral funiculus (VLF) was lower in WR vs control(p<0.001), while testosterone-treated WRs showed higher values (p < 0.05vs WRs). As regards to biceps muscle, WRs showed atrophy vs controls(p<0.05). However, the biceps muscle weight was 30% greater in testosterone-treatedWRs, in comparison to the one obtained in empty silastic-treated WRs (p<0.01).No effect of testosterone was found in controls. These preliminary data showedneuroprotective effects of testosterone in motoneuron degeneration.