Sex-specific neuroinflammatory and sociability alterations in a mouse model of autism

KAZLAUSKAS N; CAMPOLONGO M; ZAPPALA C; DEPINO AM

San Diego

Congreso; 2016 Society for Neuroscience Meeting; 2016

Society for Neuroscience

Autism is a neurodevelopmental disorder characterized by decreased sociability, impaired communication and the presence of stereotyped or restrictive behaviors. These symptoms typically appear during the first years of childhood and affect 1 in 100-200 children, with a 4:1 male:female ratio. Although many factors have been implicated in this disease, the exact underlying causes are still unclear. However, previous studies have shown a link between autism and neuroinflammation. VPA administration at GD12.5 produced decreased sociability in adult male mice, but not in females. Interestingly, we have found that adult female mice show increased micro and astroglial cell density in the cerebellum and an exacerbated peripheral inflammatory response upon a LPS challenge. However, these alterations are not present in males. We hypothesized that there is a developmental critical window in which maturation and consolidation of the neural systems responsible for autism symptoms typically occur. In order to define this temporal window, we characterized the peripheral and neuroinflammatory state of female mice from P7 to P42. We found glial alterations in the hippocampus and cerebellum of VPA mice at early ages (P21, P28 and P35). We then administered LPS during this period (P21 to P35) to further explore the direct effect of neuroinflammation on sociability in male and female mice. We found that eliciting postnatal inflammation produces distinct behavioral outcomes depending on sex.