Elucidating mechanisms underlying fever-associated rescue of behavioral phenotypes relevant to autism

  • Awarded: 2019
  • Award Type: Research
  • Award #: 626851

Fever, the increase in body temperature that follows infection, is typically associated with sickness behaviors, such as lethargy and a lack of appetite. However, for some individuals with autism spectrum disorder (ASD), fever is also correlated with an improvement in ASD-associated behavioral symptoms. Yet a mechanistic understanding of how fever-associated immune responses translate into behavioral improvements in ASD is still lacking. More specifically, it remains unknown whether it is the febrile response itself and/or other immunological signatures of inflammation that are the main drivers of this behavioral mitigation.

Viral infection during pregnancy correlates with an increased frequency of neurodevelopmental disorders in offspring, a phenomenon well studied in mice prenatally subjected to maternal immune activation (MIA).  Gloria Choi will leverage this mouse model in conjunction with an immune challenge imposed by intraperitoneal injection of lipopolysaccharide (LPS) to gain a mechanistic understanding of how fever-associated immune activation could ameliorate behavioral phenotypes relevant to ASD.

More specifically, she will 1) determine whether the MIA mouse model is a suitable system to explore the mechanisms that allow for inflammation-associated rescue of behavioral phenotypes relevant to ASD; 2) determine if the febrile response is a crucial component mediating behavioral rescue; and 3) determine if non-febrile signatures of inflammation, such as increases in cytokine levels, contribute to the behavioral rescue. Identifying the causal components involved in fever-related improvements in ASD behaviors could aid in the development of therapeutic interventions for ASD.

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