Autism spectrum disorder (ASD) is a highly prevalent psychiatric disorder. Both genetic and environmental factors are involved in ASD etiology. Recently we reported the molecular and physiological role of an ASD high-risk gene, Cortactin-binding protein 2 (CTTNBP2) from mouse genetic models. We showed that Cttnbp2 deficiency leads to aberrant social interaction, one of the core symptoms of ASD. Proteomic and immunoblotting analyses further revealed that a set of ASD-associated genes, including SHANKs and NMDAR, are down-regulated in Cttnbp2 deficiency synaptosomal fraction. Administration of D-cycloserine (DCS, an NMDAR coagonist) improves social behavior defects of CTTNBP2 deficiency models further validates the involvement of NMDAR signaling in CTTNBP2 regulated social behaviors. In addition, zinc association is also one of the convergent features in differentially expressed proteins identified in Cttnbp2 deficient synaptosomal fractions. The concentration of zinc in Cttnbp2 deficient brain tissue is also reduced. Seven days of zinc supplementation improved social behaviors of Cttnbp2 deficient models. These results suggest, as a genetic factor, Cttnbp2 interacts with zinc, an environmental factor in the regulation of social behaviors. Our model provides an example of genetic and environmental factor interaction in ASD etiology.
ISSN 2719-1990 (Print)
Philippine E-Journals
