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

CECILIA ZAPPALA; NADIA KAZLAUSKAS; AMAICHA DEPINO; MARCOS CAMPOLONGO

San Diego

Congreso; Society for Neuroscience Annual Meeting 2016; 2016

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, theexact underlying causes are still unclear. However, previous studies have shown a link betweenautism and neuroinflammation. VPA administration at GD12.5 produced decreased sociability inadult male mice, but not in females. Interestingly, we have found that adult female mice showincreased micro and astroglial cell density in the cerebellum and an exacerbated peripheralinflammatory response upon a LPS challenge. However, these alterations are not present inmales. We hypothesized that there is a developmental critical window in which maturation andconsolidation of the neural systems responsible for autism symptoms typically occur. In order todefine this temporal window, we characterized the peripheral and neuroinflammatory state offemale mice from P7 to P42. We found glial alterations in the hippocampus and cerebellum ofVPA mice at early ages (P21, P28 and P35). We then administered LPS during this period (P21to P35) to further explore the direct effect of neuroinflammation on sociability in male andfemale mice. We found that eliciting postnatal inflammation produces distinct behavioraloutcomes depending on sex.