Autism spectrum disorder (ASD) is seen as a collection of disorders that is predominantly developmental in nature and largely genetic in origin. However, there is tentative evidence to support the idea that fever can improve symptoms in individuals with ASD, which suggests that behavioral symptoms could improve transiently under certain conditions. This implies that the circuits affected in ASD possess the structural integrity to perform relatively normally under certain conditions. Fever could conceivably improve brain function in ASD through elevated body and brain temperature. Alternatively, changes to brain function may be a result of the inflammatory response that underpins fever.

Colm Cunningham proposes to dissociate fever from its normal, inflammatory underpinnings in order to compare these different environmental paradigms for their effects on brain and body temperature, brain energy metabolism and neuronal activation. These experiments will be performed in mice. Findings from these studies will allow Cunningham and his colleagues to identify what is common among these perturbations and what is distinct.

In subsequent experiments, he plans to use mouse models relevant to ASD (including SHANK3B^-/-, TSC2^+/- and C58/J) to assess whether hyperthermia or systemic inflammation can reverse key deficits in these models. Cunningham’s team will assess whether these environmental perturbations produce significant changes in brain inflammatory and autophagic pathways in wild-type animals, as a prelude to more substantial mechanistic studies in these ASD models.

This work will help advance our understanding of the specific mechanisms affected by fever that allow for transient optimal circuit performance in ASD. Such findings may lead to potential new approaches for improving cognitive and behavioral symptoms in individuals affected by ASD.