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.