Abstract
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, with delayed or altered language development, and repetitive and stereotypic behavior. Although the gene-environment interactions are thought to contribute to many case of autism, little is know about these mechanisms. To understand the gene-environment interactions in autism, we focused to analyze Secretin (Sct) and secretin receptor (Sctr) deficient mice. Sct is a member of the secretin/VIP/glucagon peptide hormone family, and Sctr is a G-protein coupled receptor. Several clinical trials on Sct administration report neurobehavioral improvement in autism and schizophrenia although the results of these trials remain controversial. Sct and Sctr deficient mice showed abnormal autism-related social and repetitive behavior with impaired synaptic plasticity in hippocampus. In addition, the mutant mice exhibited mildly diminished survival of neural progenitor cells/immature neurons. Furthermore, we identified secretin signal plays a neuroprotective role of neuronal progenitor cells against the neurotoxicity of ethanol.
Our data demonstrate that Sct and Sctr mutant mice are useful animal models of autism and could identify the environ-mental risk factors that develop autismrelated phenotypes. Knowing the gene-environment interactions in neuropsychological development will shed light on the molecular mechanism of autism and potentially point toward therapeutic strategies.
