MUSCLE TROPHISM AFTER TESTOSTERONE TREATMENT IN THE WOBBLER MOUSE, AN SPONTANEOUS MODEL FOR AMYOTROPHIC LATERAL SCLEROSIS (ALS).

AGUSTINA LARA; MARIA MEYER; ESPERANTE IVAN; GONZALEZ DENISELLE, MARIA C.; ALEJANDRO F. DE NICOLA; GARAY, LAURA I.

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigacion Clnica

Abstract/Resumen: Patients suffering amyotrophic lateral sclerosis (ALS) present muscle atrophy in upper and lower limbs and difficulties in swallowing and dysarthria in association to motoneuron degeneration. Wobbler mice (WR) are animal models of ALS showing selective loss of motoneurons, astrocytosis and microgliosis in the ventral horn of the cervical spinal cord, brain stem and motor cortex. The incidence of ALS is greater in men than in fertile women; however, it increases after menopause. Therefore, sex steroid hormones could be involved in disease susceptibility or outcome. Previously, we demonstrated that testosterone treatment to WRs reduced astrocytosis and increased glutamine synthetase immunoreactivity, an enzyme necessary for maintaining glutamate concentration in synaptic cleft. Now, we investigated the effect of testosterone treatment on myelination and muscle trophism. Treatment consisted of 10 mm silastic tubes containing crystalline testosterone s.c. for 2 months to male symptomatic WR. Non-treated WR or control received an empty silastic tube s.c. Testosterone serum levels and seminal vesicles weight were significantly higher in testosterone-treated WRs compared to empty silastic-treated WRs (p<0.01). Luxol fast blue (LFB) staining was used to identify myelin. We quantified the % of area stained over a threshold in white matter of the cervical cord. Significant group differences were shown by ANOVA (F(3,16)= 29.86, p<0.001) in the % of stained area for LFB in the ventrolateral funiculus (VLF). Lower LFB staining was shown in WRs (mean ± SEM-WR: 27.56 ± 5.57 vs. control: 87.40 ± 0.92; p<0.001), while higher values were demonstrated after testosterone treatment (WR+testosterone: 41.94 ± 5.62 vs. WR, p<0.05). As regards to biceps muscle mass, one way ANOVA also indicated significant group differences (F(3,24)= 7.55, p<0.01). WRs showed biceps atrophy (WRs: 0.62 ± 0.08 mg/g body weight vs. controls: 0.86 ± 0.04, p<0.05). However, greater mass was shown in testosterone-treated WRs in comparison to empty silastic-treated WRs (WR+testosterone: 1.05 ± 0.08, p<0.01 vs. WR). No effect of testosterone treatment was found in controls. These preliminary data showed protective effects of testosterone in motoneuron degeneration.