Inflammation and the autistic brain

AMAICHA M. DEPINO

Buenos Aires

Encuentro; Advanced Molecular Biology: the EMBL in Argentina 2012; 2012

Several reports have associated peripheral and central alterations in the inflammatory and immune responses with autism spectrum disorders (ASD). However, the consequences of these inflammatory processes on the behavioral symptoms of ASD have not been extensively studied. We used two experimental paradigms to try to elucidate the role of brain inflammation on ASD. On the one hand, we evaluated the central and peripheral responses to an inflammatory stimulus in a mouse model of autism. Mice prenatally exposed to valproic acid (VPA) show reduced levels of sociability in adulthood. We found that these mice also show signs of neuroinflammation and an exacerbated inflammatory response when challenged with LPS. On the other hand, we studied the effect of expressing the anti-inflammatory cytokine TGF-beta1 in the dentate gyrus of the mouse. TGF-beta1 was previously found to be augmented in the brain of autistic patients. We found that the postnatal expression of this cytokine leads to autism-related behaviors in the adult mouse, but adult expression have the opposite effect. Our results support then a role of brain inflammation on both the etiology and pathophysiology of ASD.