Identifying molecular mediators of the effects of cerebellar neuroinflammation on sociability: relevance for autism

VARELA M; ZAPPALA C; DEGIORGI S; SEIFFE A; DEPINO AM

Villa Carlos Paz

Congreso; XXXIV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

Sociedad Argentina de Investigación en Neurociencias

One of the main symptoms of autism spectrum disorder (ASD) is the difficulty to engage socially. Although the pathophysiological bases of ASD are unknown, there is vast evidence on the role of the cerebellum in the development and expression of the disorder. We have reported that inflammation in the lobule 7 of the mouse cerebellum, induced by the stereotaxic injection of lipopolysaccharides (LPS), results in a decrease in sociability 24 hours after. This effect is prevented completely by dexametasone and partially by ibuprofen. The aim of this project is to identify mediators of these effects by detecting inflammatory molecules that can alter sociability in ASD. To perform this, groups of adult male CF1 mice were injected with either 10ng LPS (LPS group) or saline (SAL group) in cerebellum lobule 7. 30 minutes before, both groups will receive dexamethasone, ibuprofen, or saline. Thus, the experimental design evaluates the effects of drugs (DEXA; IBU; SAL) on the treatment (LPS; SAL). In these animals, we observed that DEXA has a more pronounced effect than IBU in blocking microglia activation. We will further characterize the response, by identifying the expression of pro and anti-inflammatory cytokines in the cerebellum of LPS injected and anti-inflammatory treated mice. To this aim, we will quantify the expression of pro and anti-inflammatory cytokines by RT-PCR. The goal of this work is the identification of possible therapeutic targets for individuals with ASD.