MitoQ attenuates maternal immune activation-induced mitochondrial and ER stress programs and ameliorates psychiatric-like behavioral deficits.

Maternal immune activation (MIA) increases risk for neurodevelopmental and psychiatric disorders, yet the stress programs linking prenatal immune challenge to persistent neuronal dysfunction remain incompletely defined. Here, we show that MIA engages convergent oxidative and ER stress programs accompanied by mitochondrial dysfunction across brain regions. Transcriptomic profiling of offspring hippocampus (HIP) revealed coordinated downregulation of oxidative phosphorylation (OXPHOS) and upregulation of ER protein-processing pathways, consistent with increased neuronal oxidative damage and ER stress markers. In parallel, hippocampal neurons exhibited mitochondrial fragmentation, reduced membrane potential, and a marked reduction in respiratory capacity. In the prefrontal cortex (PFC), MIA induced broad transcriptional remodeling that again highlighted ER stress-related pathways together with a region-specific OXPHOS signature, and these changes were accompanied by mitochondrial structural abnormalities and elevated inflammatory signaling. Finally, the mitochondria-targeted antioxidant MitoQ restored mitochondrial respiration and ameliorated anxiety-like and social behavioral abnormalities in MIA offspring. Together, these findings identify mitochondrial redox imbalance as a mechanistic node linking prenatal immune challenge to circuit-relevant cellular stress programs and support mitochondrial redox modulation as a potential intervention strategy.