Social behavior and influence of the immune system in a mouse model of autism.

摘要

Autism is a common neurodevelopmental disorder with an unknown cause or cure. Impairments in social behavior constitute a diagnostic symptom of autism along with communication deficits and repetitive behaviors. There are no biomarkers for autism, meaning that there are no indicators in blood tests, lumbar punctures or body scans that can assist in diagnosis of the disorder. Factors contributing to the emergence of autistic behaviors have been identified; however, effective treatment strategies remain elusive. Therefore, diverse research approaches are necessary to reveal mechanisms underlying this highly prevalent disorder.;Mouse models, while unable to replicate human conditions, provide distinct advantages in testing causal hypotheses of disorders. Ideal mouse models for autism display social impairments, communication deficits and repetitive behaviors; however, designing tasks to measure such behaviors presents a unique challenge. A major strength of this laboratory has been in identifying and characterizing behavioral phenomena in rodents. Using knowledge of the natural environment and behavior of the mouse, this laboratory established and adapted several tests to measure behaviors relevant to autism. From these tests, this laboratory and others have found that the BTBR T+tf/J (BTBR) mouse strain displays behaviors that are consistent with those observed in autism.;This dissertation demonstrates that BTBR mice show social avoidance, as well as a pattern of behavior analogous to gaze aversion observed in autism, when in closely confined conditions. BTBR mice also display a normal-to-low anxiety profile, suggesting that anxiety is not a primary contributing factor in the social deficits of this strain. In addition, this dissertation shows that immune activation in pregnant mouse dams from a high sociability strain produces autism-relevant behavioral deficits in offspring. Finally, the dissertation shows that the placental gene expression of an immune pathway is altered in BTBR mice, which is suggestive of impaired prenatal regulation of immune signaling in this mouse model of autism.