Publication date: Jul 01, 2025
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by a variety of factors. Our previous study indicated that hypoxia-inducible factor 1 alpha (HIF-1α) plays a role in hypoxia-caused autism-like behavior. In this study, we investigated the mechanism by which HIF-1α contributes to prenatal hypoxia-induced autism-like behavior in vivo to provide an experimental basis for the treatment of ASD. We established a prenatal hypoxia model of pregnant rats by placing 17-day pregnant rats into a self-made hypoxia chamber filled with a nitrogen containing 10 %+/-0. 5 % oxygen. Within 24 h after birth, the lateral ventricles of the prenatal hypoxia offspring rats were injected with a recombinant adeno-associated virus designed to silence HIF-1α expression. The autistic behavior of offspring rats in the HIF-1α silenced group was significantly alleviated compared with that of the prenatal hypoxia group. With the silencing of HIF-1α, the activity of phosphatase and tensin homolog (PTEN) increased and the PI3K/AKT pathway was inhibited by negative feedback. The mRNA expression level of vascular endothelial growth factor (VEGF) was decreased in the Si-HIF-1α silenced group and N-methyl D-aspartate receptor subtype 2 (NR2A) expression was downregulated. Thus, our study indicates that HIF-1α plays a role in hypoxia-induced autism-like behavior, and its regulatory effect may be achieved by inhibiting the activity of PTEN, resulting in activation of the PI3K signaling pathway. Synaptic plasticity regulation may also be involved.
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | hypoxia |
| disease | MESH | autism |
| disease | MESH | Autism spectrum disorder |
| disease | MESH | neurodevelopmental disorder |
| drug | DRUGBANK | Nitrogen |
| drug | DRUGBANK | Oxygen |
| disease | MESH | Disease Models Animal |
| pathway | REACTOME | Signal Transduction |