Neuroinflammation in autism. An experience from an experimental model

AMAICHA DEPINO

La Habana

Congreso; Restauracion Neurologica 2014; 2014

Centro Internacional de Restauracion Neurologica

Clinical reports on immunological alterations and chronic inflammatory diseases in autistic individuals have prompted many studies on the role of the inflammatory response in autism spectrum disorders (ASD). In this context, the use of animal models has many advantages, as systems can be more easily manipulated and evaluated. We have used two experimental paradigms to evaluate the role of brain inflammation on ASD. On the one hand, we analyzed 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. Moreover, we found cerebellar microgliosis and showed that an LPS injection into the lobule VII of the murine cerebellum results in reduced sociability. On the other hand, we tested the effect of expressing the anti-inflammatory cytokine TGF-beta1 in the hippocampus of the mouse. TGF-beta1 is 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, but they also highlight the complexity of this link. We consider that a clearer picture on the temporal and regional effects of brain inflammation can contribute to a better understanding of ASD.