CONICET | Buscador de Institutos y Recursos Humanos

Autism is a neurodevelopmental disorder characterized by impairments in communication, decreased socialinteraction and stereotyped or restrictive behaviors. Although genetic, epigenetic and environmental factorshave been implicated in this disease, the exact underlying causes are still unclear.As previous studies have shown a link between autism and neuroinflammation, our working hypothesis isthat central inflammatory processes and particularly glial activation could be responsible for the behavioralphenotype. We hypothesized that there is a developmental critical window in which maturation andconsolidation of the neural systems responsible for these symptoms typically occur.The administration of VPA at GD 12.5 is used as an autism model in mouse. Using this model, we detectedan activated glial state in the cerebellum and the hippocampus of adult mice, besides early and adultbehavioral alterations. The aim of this work is to identify the specific time window when inflammationappears and to study its correlation with the behavioral phenotype that we observe.We characterized the central inflammatory state studying astro and microglial density from P7 to P42 usingimmunofluorescence analysis. We found glial alterations in the hippocampus (CA1 and DG): higher GFAP+density and activated microglia starting at P21 and in some areas remaining until P35. Interestingly, this wasnot the case for the cerebellum: we found fewer activated microglial cells at P28 and P35. Also, weevaluated the peripheral inflammatory response by means of measuring corticosterone levels after a LPSchallenge and found that VPA mice showed a normal response postnatally.We are modulating the neuroinflammatory state during this critical period with both anti and proinflammatory treatments, using minocycline and LPS respectively. These experiments will allow us to testthe direct effect of the neuroinflammatory state in the autism related behaviors that we observe in the VPAmodel.