Gestational B-vitamin supplementation alleviates PM-induced autism-like behavior and hippocampal neurodevelopmental impairment in mice offspring.
Ecotoxicol Environ Saf. 2019 Dec 15 ;185:109686. Epub 2019 Sep 20. PMID: 31546205
Gestational exposure to PMis a worldwide environmental issue associated with long-lasting behavior abnormalities and neurodevelopmental impairments in the hippocampus of offspring. PMmay induce hippocampus injury and lead to autism-like behavior such as social communication deficits and stereotyped repetitive behavior in children through neuroinflammation and neurodegeneration. Here, we investigated the preventive effect of B-vitamin on PM-induced deleterious effects by focusing on anti-inflammation, antioxidant, synaptic remodeling and neurodevelopment. Pregnant mice were randomly divided into three groups including control group (mice subject to PBS only), model group (mice subject to both 30 μL PMof 3.456 μg/μL and 10 mL/(kg·d) PBS), and intervention group (mice subject to both 30 μL PMof 3.456 μg/μL and 10 mL/(kg·d) B-vitamin supplementation (folic acid, vitamin B6 and vitamin B12 with concentrations at 0.06, 1.14 and 0.02 mg/mL, respectively)). In the current study B-vitamin significantly alleviated neurobehavioral impairment reflected in reduced social communication disorders, stereotyped repetitive behavior, along with learning and spatial memory impairment in PM-stimulated mice offspring. Next, B-vitamin corrected synaptic loss and reduced mitochondrial damage in hippocampus of mice offspring, demonstrated by normalized synapse quantity, synaptic cleft, postsynaptic density (PSD) thickness and length of synaptic active area. Furthermore, significantly down-regulated expression of pro-inflammatory cytokines including NF-κB, TNF-α and IL-1β, and lipid peroxidation were found. We observed elevated levels of oxidant-related genes (SOD, GSH and GSH-Px). Moreover, decreased cleaved caspase-3 and TUNEL-positive cells suggested inhibited PM-induced apoptosis by B-vitamin. Furthermore, B-vitamin increased neurogenesis by increasing EdU-positive cells in the subgranular zone (SGZ) of offspring. Collectively, our results suggest that B-vitamin supplementation exerts preventive effect on autism-like behavior and neurodevelopmental impairment in hippocampus of mice offspring gestationally exposed to PM, to which alleviated mitochondrial damage, increased anti-inflammatory and antioxidant capacity and synaptic efficiency, reduced neuronal apoptosis and improved hippocampal neurogenesis may contribute.