Abnormal social behaviors in young and adult rats neonatally infected with Borna disease virus

Autism spectrum disorders (ASD) have been the focus of a great deal of research and clinical speculation. This intense interest relates to both the perplexing pathogenesis and devastating consequences of these disorders. One of the obstacles to understanding the pathogenesis of autism and to developing efficient treatment has been the paucity of animal models that could be used for hypotheses-driven mechanistic studies of abnormal brain and behavior development and for the pre-clinical testing novel pharmacological treatments. In this report, we briefly review our animal model of ASD based on neonatal Borna disease virus (BDV) infection and present new data about abnormal social interaction in adult BDV-infected rats. We found that neonatal BDV infection profoundly affected social behaviors in adult rats. Compared to the control rats, both 90- and 180-day-old infected rats spent less time in active social interaction and more time in following their partners. In the intruder-resident test, the BDV-infected resident rats exhibited less aggression towards the intruders and showed more the following-the-intruder behavior. The following-the-partner behavior may be an example of "stereotypic" activity due to BDV-induced abnormal social communication between rats. The previously published results and present findings indicate that neonatal BDV infection significantly altered the normal pattern of social interaction in rats. Co-localization of activated microglia and dying Purkinje cells in BDV-infected rats suggests that the BDV model could be used to study a pathogenic link of Purkinje cell dropout and neuroinflammation to abnormal social behaviors.