Study of peripheral and central inflammatory responses in a mouse model of autism

KAZLAUSKAS N; LUCCHINA L; CAMPOLONGO M; DEPINO A

Cancún

Congreso; International Society of Neurochemistry 2013; 2013

International Society of Neurochemistry

Autism is a neurodevelopmental disorder with an early onset, during the first years of childhood. The symptoms include impairments in social interaction and communication, and repetitive and stereotyped behaviors. We hypothesized that there is a developmental critical window in which maturation and consolidation of the neural systems responsible for these symptoms typically occur and that they are altered in the patients. The exact underlying causes of autism are still unclear, and although previous studies have shown a link between autism and neuroinflammation, there is no evidence of a direct effect. Our working hypothesis is that central inflammatory processes and glial activation in particular could be responsible for the behavioral phenotype, representing an underlying common factor in the different proposed etiologies of autism. The prenatal exposure to valproic acid (VPA) is associated with the development of autistic symptoms in humans. Using a mouse model of autism (injection of VPA at the gestational day 12.5), we detected early and adult effects of VPA on behaviors relevant to autism. Moreover, we found that VPA exposure results in an activated glial state in the cerebellum and the hippocampus of adult mice. The aim of this work is to identify the specific time window when inflammation appears in the VPA postnatal brain and to study if this correlates with the behavioral effects that we observe. We characterized the astro and microglial state in the early postnatal period (from P7 to P42) by means of immunofluorescence analysis. Additionally, as we have found that VPA mice show an exacerbated inflammatory response to a LPS injection in adulthood, we analyzed the postnatal HPA axis function by means of measuring corticosterone levels after a LPS challenge. The identification of a critical window when inflammation is altered in VPA mice will allow us to test the specific hypothesis of whether modulating inflammation during the postnatal period can revert the prenatal effects of VPA on social behavior.