NF-κB Signaling in the Brain of Autistic Subjects

Autism is a neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic and inflammatory mechanisms may contribute to the pathogenesis of this disorder. Nuclear factor- κ B (NF- κ B) is an important gene transcriptional factor involved in the mediation of inflammation and apoptosis. This study examined the activities of the NF- κ B signaling pathway in the brain of autistic subjects and their age-matched controls. The NF- κ B activation is also determined in the brain of BTBR mice, which is a promising animal model for study of pathogenic mechanisms responsible for autism. Our results showed that the level of IKK α kinase, which phosphorylates the inhibitory subunit I κ B α , is significantly increased in the cerebellum of autistic subjects. However, the expression and phosphorylation of I κ B α are not altered. In addition, our results demonstrated that the expression of NF- κ B (p65), and the phosphorylation/activation of NF- κ B (p65) at Ser536 are not significantly changed in the cerebellum and cortex of both autistic subjects and BTBR mice. Our findings suggest that the NF- κ B signaling pathway is not disregulated in the brain of autistic subjects and thus may not be significantly involved in the processes of abnormal inflammatory responses suggested in autistic brain.