Postnatal alterations in neuroglia are not accompanied by an altered peripheral inflammatory response in an animal model of autism

NADIA KAZLAUSKAS; LUCIANA LUCCHINA; MARCOS CAMPOLONGO; AMAICHA DEPINO

New York

Workshop; Workshop on Autism Spectrum Disorders ? Cold Spring Harbor Laboratory; 2015

Cold Spring Harbor Laboratory

Autism is a neurodevelopmental disorder characterized by impairments in communication, decreased social interaction and stereotyped or restrictive behaviors. Although genetic, epigenetic and environmental factors have 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 is that central inflammatory processes and particularly glial activation could be responsible for the behavioral phenotype. We hypothesized that there is a developmental critical window in which maturation and consolidation 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 detected an activated glial state in the cerebellum and the hippocampus of adult mice, besides early and adult behavioral alterations. The aim of this work is to identify the specific time window when inflammation appears 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 using immunofluorescence 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 was not the case for the cerebellum: we found fewer activated microglial cells at P28 and P35. Also, we evaluated the peripheral inflammatory response by means of measuring corticosterone levels after a LPS challenge and found that VPA mice showed a normal response postnatally.We are modulating the neuroinflammatory state during this critical period with both anti and pro-inflammatory treatments, using minocycline and LPS respectively. These experiments will allow us to test the direct effect of the neuroinflammatory state in the autism related behaviors that we observe in the VPA model.