Developmental Brain Injury Associated with Abnormal Social behaviors in Neonatally BDV-Infected Rats: A Model for Autism




M. Pletnikov,

S. Rubin, T. Moran, K. Carbone*. Food and Drug Administration,

Rockville, MD

Autism is a common developmental

disease of children, resulting in abnormalities in social

behavior (e.g., play) as well as neurological (e.g., sensorimotor

deficits) and neuroanatomical (e.g., cerebellar neuron deficits)

disease. Viruses are a known etiologic agent of autism, such as

rubella, HIV and HSV.

We have previously described

neurological and neuroanatomical deficits in our neonatally Borna

disease virus infected rat model. A review of these abnormalities

suggested a similar pathogenesis to those abnormalities described

in autistic children. Thus, we engaged in behavioral analysis of

these rats to explore the possibility that evidence of

characteristic social abnormalities (e.g., play behavior) were

present. Play behavior, non-social exploratory activity and

non-play social interaction were observed in neonatally

BDV-infected juvenile rats. Using the

“intruder-resident” paradigm, four experimental

pairings of infected (BDV) and uninfected (NL) rats were studied

as follows: NL-NL; NL-BDV; BDV-NL; and BDV-BDV (the first member

is the resident the second member is the intruder). Non-social

exploratory activity was similar in BDV and NL residents.

Duration of non-play social investigation was higher in BDV

residents compared to NL residents on the first test day, but no

difference was found between groups on the second test day. When

confronted with NL intruders, NL residents exhibited

significantly more play behavior compared to the NL-BDV, BDV-NL

and BDV-BDV pairs, when play behavior was measured by the number

of “pins”. Moreover, overall, NL residents demonstrated

higher play soliciting behaviors than BDV-residents, indicating

attenuated readiness to play in BDV rats. The number of pins and

play solicitations in BDV-NL pairs significantly increased over

two days of testing, while play activity in NL-BDV pairs declined

on the second test day. In a setting of neuroanatomical and

neurological deficits concordant with autism, these data support

the value of the neonatally BDV-infected rat model for the study

of autism.