Effect of postnatal mynocicline treatment on a two-hit model of autism in female mice

SEIFFE A; RAMIRES MF; DEGIORGI S; SALGUEIRO N; ZAPPALA CM; DEPINO AM

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Autism spectrum disorders (ASD) are characterized by reduced sociability, diminished communicative skills and repetitive behaviors. Notably, the proportion between boys and girls diagnosed with ASD is 4:1 approx. This suggests a higher susceptibility in boys to develop ASD, or resilience in girls. To identify the biological mechanisms underlying this bias, we used a mouse model of ASD: the prenatal exposure to valproic acid (VPA). Remarkably, this model also presents a different phenotype in males and females, as females do not show the reduction in sociability observed in adult males.One important risk factor in ASD is immune system dysregulation. In fact, we found that prenatal exposure to VPA leads to alterations in microglia and astrocytes in females between postnatal day (PD) 21 and 35. Using a two-hit model, which consists in prenatal VPA exposure and a chronic treatment with LPS between PD 21 and 35, we found that female mice express a reduction in sociability. This evidence suggests that immune alterations during this postnatal period are critical to develop social alterations and may overcome the sex-dependent resilience.Minocycline is an antibiotic that crosses the blood?brain barrier and acts by reducing the microgliosis. We hypothesized that Minocycline administration during the critical period mentioned above can revert the behavioral alterations observed in our two-hit model.