Postdoctoral Scholars Association

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex etiology involving genetic, environment, and gene-environment interactions. We recently discovered a novel gene, NHIP (neuronal hypoxia inducible, placenta), that has decreased expression in ASD placenta and brain. Its transcript levels increase in the human neuronal cell line LUHMES following differentiation and exposure to hypoxia, suggesting that it may play a protective role during hypoxia-induced oxidative stress. Through immunoprecipitation of biotinylated NHIP peptide, we identified methyl-CPG-binding protein 2 (MeCP2) as a potential NHIP binding partner. Loss of MeCP2 leads to Rett Syndrome (RTT), and reduced expression is associated with ASD. Many RTT patients display breathing abnormalities that lead to intermittent hypoxia. We hypothesize that NHIP may interact with MeCP2 to promote proper hypoxia response. To assess the role of NHIP in hypoxia-induced oxidative stress,

we added exogenous NHIP peptide to LUHMES 24 hours prior to 1% hypoxia treatment and observed that ROS levels decreased with NHIP treatment. We also stained for NHIP and MeCP2 to observe their interaction in LUHMES under hypoxia conditions. Characterization of NHIP and its binding partners will allow for evaluation of its potential use as a neuroprotective therapeutic in neurodevelopmental disorders such as ASD.