Autism is a neurodevelopmental syndrome defined by deficits in social reciprocity and communication and by unusual repetitive behaviors. While there is clearly an underlying genetic predisposition, the etiology(ies) of autism is/are currently unknown. Development of animal models of autism have been hobbled by the lack of knowledge concerning its etiology(ies) and by the paucity of data on the characteristic neuropathology of autism, i.e., it is not clear what a successful model of autism would look like. If one focuses on the root deficit in autism, i.e., the impairment of social interaction, however, successful mouse and nonhuman primate models are achievable. The overarching goal of this project is to establish batteries of behavioral tasks that will provide sensitive assessments of normal mouse and rhesus monkey social behavior. With the establishment of the animal models, two hypotheses will be tested: 1) that prenatal and/or postnatal exposure to xenobiotics will decrease normal conspecific social behavior; and 2) that changes in social behavior will be associated with alterations of brain regions, such as the amygdala, that have been implicated in social behavior. Perinatal mice will be parametrically exposed to thimerosal, methyl mercury, and to a mixture of PCB congeners (PCB 153, 180, 118, 138, and 170) to determine whether these xenobiotics alter normal social behavior. Based, in part, on the mouse studies and on information concerning expected environmental exposure in autistic children, neonatal monkeys will also be exposed to thimerosal, methyl mercury and PCBs. The mouse battery of social and cognitive testing will include: Response to maternal separation and relocation; response to maternal separation and relocation; response to novel objects; response to a human intruder; response to social videotapes. A specially designed ethogram will also be used to evaluate maternal < - >infant interactions and to study the emergence and quality of social behaviors through daily dyadic social interactions with """"""""stimulus"""""""" animals. At the termination of behavioral testing, morphological changes will be evaluated in brain regions, such as the amygdala, known to be involved in normal social behavior. Additional tissue will be distributed to Core I for analysis of xenobiotic distribution, to Core II for analysis of cytokines and autoantibody production and Core III for altered brain gene expression.
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