ADMINISTRATION OF ANASTRAZOLE, AN AROMATASE INHIBITOR, REDUCES THE PROTECTIVE EFFECTS OF TESTOSTERONE TREATMENT IN AN ANIMAL MODEL OF AMYOTROPHIC LATERAL SCLEROSIS

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

Congreso; LXVI Reunión Científica de la Sociedad Argentina de Investigacion Clinica,; 2021

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motoneurons leading to muscle weakness and motor impairment. The Wobbler (WR) mouse, a recognized model of ALS, shows a selective loss of motoneurons, astrocytosis and microgliosis in cervical spinal cord (CSC). ALS presents in men at younger ages than women, but increases after menopause. Testosterone (T) exerts its effects via androgen (AR), or estrogen receptors after bioconversion into several metabolites. Previous work has shown that T reduces gliosis and improves clinical score in male WRs. Now, we investigated the effects of cotreatment of T + anastrazole, an aromatase inhibitor (AI), on: 1) mRNA expression of myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP)- 2) CD11B mRNA, a marker of microglia, 3) % AR-immunoreactive (IR) cells in ventral horn. T was implanted in 10mm silastic tubes for 2 months. AI was given in DMSO 10% by Alzet osmotic pumps (1mg/kg/day) s.c. starting 1 week before T. Four groups were prepared: a) WRs or (b) controls receiving empty silastic tubes + vehicle-pumps, c) WR+T (silastic tubes filled with T) + vehicle-pumps and d) WR+T+AI. Pituitary weight, a gland sensitive to estradiol, is greater in WRs (p