Abstract
Epidemiological studies have shown that not only genetic factors, but also environmental factors contribute to the risks of development of neurodevelopment disorders, including autistic spectrum disorder (ASD). For example, premature birth is regarded as one of the environmental risk factors, since many survivors of extremely preterm infants (born before 28 weeks of gestation) develop ASD in later life. Among environmental risk factors, infection-induced maternal immune activation during pregnancy is thought to play the pathogenesis of neurodevelopmental disorders, such as ASD and schizophrenia. Recently, investigations in animal models of maternal immune activation revealed local changes in the brain tissue architecture in the offspring. Interestingly, similar changes in brain tissue architecture have also been reported in human ASD patients. On the other hand, it is unclear how these architectural changes contribute to the pathophysiology of ASD. We used newly established mouse models to analyze how brain architectural changes are involved in the pathogenesis of ASD. Our findings suggest that local changes in the brain tissue architecture affect distant brain regions, giving rise to abnormal animal behaviors. However, the mechanisms underlying how local changes in the brain tissue architecture affect the overall brain activities and lead to behavioral abnormalities still remain unclear.
