Serotonin, CAM Expression and Toxins During Development

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DESCRIPTION: (provided by applicant): Behavioral deficits following exposure to different neurotoxicants during development may be manifested as a delay in onset of a behavior, a regression of a previously articulated behavior to performance seen earlier in development (before the normal onset or development of the behavior), or intrusions of unusual or aberrant behaviors which replace those behaviors normally seen at developmental time points. These behavioral deficits, which are all seen in clinical cases of children with autism or pervasive developmental disorders, may be the result of late postnatal or early neonatal exposure to neurotoxicants. The aims of the current research project include a) characterize normal development of behaviors related to cerebella, striatal and hippocampal development through behavioral testing and changes in cell adhesion molecules (CAMs); b) administer methylmercury and sodium valproate to animals just prior or just following the normal ontogeny of these behaviors in order to determine critical periods of brain development which these compounds affect; c) link normal and aberrant development of these behaviors to regional changes neurochemistry as well as alterations in CAM levels and CAM mRNA in discrete brain areas, as well as assessing the neurotoxic potential of these compounds using an assay which is independent from changes in cell adhesion proteins d) assess sensitivity of treated animals to later challenge with agents which may potentially exacerbate deficits, produce intrusions in behavior, or alleviate functional deficits and reverse altered cell adhesion molecule expression.