Autism is a multi-causal developmental disorder that is behaviorally defined by impairments in reciprocal social interaction, communication deficits, and restricted or stereotyped interests and actions. In this study, I will use two different strategies towards modeling autism in non-human primates. For the first strategy, an accepted cause of autism symptomatology in humans, phenylketonuria (PKU), will be studied in rhesus monkeys. To this end, I will use an approach that has previously been demonstrated to cause social and cognitive deficits in rhesus monkeys, the exposure of fetal monkeys to hyperphenylalaninemia through the delivery of a high phenylalanine diet to pregnant monkeys. These hyperphenylalaninemic monkeys will provide a potentially reliable model in which the behavioral phenotype and neuropathology of autism can be explored. For the second strategy, the potential causative effects of maternally-transferred antibodies directed at brain will be explored by exposing fetal monkeys to antibodies collected from mothers of children with autism. Following birth, both the hyperphenylalaninemic and antibody-exposed monkeys will be tested for neurological, physiological, and behavioral impairments through a battery of tests aimed at identifying autistic-like traits in monkeys. After the completion of testing, the brains of the hyperphenylalaninemic monkeys will be histologically analyzed for the presence of neuropathology. Through this research, I hope to establish animal models in which to explore the neuroanatomical correlates of autistic behavior, and in doing so, identify a causal role for maternal neuronal antibodies in a subset of autism cases.
