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Gestational B-vitamin supplementation alleviates PM2.5-induced autism-like behavior and hippocampal neurodevelopmental impairment in mice offspring
Open accessAbstract
Gestational exposure to PM2.5 is a worldwide environmental issue associated with long-lasting behavior abnormalities and neurodevelopmental impairments in the hippocampus of offspring. PM2.5 may 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 PM2.5-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 PM2.5 of 3.456 μg/μL and 10 mL/(kg·d) PBS), and intervention group (mice subject to both 30 μL PM2.5 of 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 PM2.5-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 PM2.5-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 PM2.5, to which alleviated mitochondrial damage, increased anti-inflammatory and antioxidant capacity and synaptic efficiency, reduced neuronal apoptosis and improved hippocampal neurogenesis may contribute.
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B-vitamin supplementation (folic acid, vitamin B6 and vitamin B12) significantly alleviated neurobehavioral impairment in offspring exposed to PM2.5 during gestation.
“In a mouse model, B-vitamin supplementation (folic acid, vitamin B6 and vitamin B12) significantly alleviated neurobehavioral impairment in offspring exposed to PM2.5 during gestation [223].”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [223]
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Johnson, N. M., Hoffmann, A. R., Behlen, J. C., Lau, C., Pendleton, D., Harvey, N., Shore, R., Li, Y., Chen, J., Tian, Y., et al. (2021) · Environmental Health and Preventive Medicine · doi:10.1186/s12199-021-00995-5 · Cited by 339
Metadata
- Authors
- Wang, T., Zhang, T., Sun, L., Li, W., Zhang, C., Yu, L., & Guan, Y.
- Affiliations
- Weifang Medical University (CN)
- Harvard University (US)
- Corresponding author
- Yu, Li
- Guan, Yingjun
- Venue
- Ecotoxicology and Environmental Safety
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 185
- Pages
- 109686
- ISSN
- 0147-6513 (ISSN-L)
- OpenAlex
- W2974586741
- Cited by
- 55
- References
- 5
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 11 · 2021: 7 · 2020: 5
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Ecotoxicology and Environmental Safety (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Shandong Provincial Natural Science Foundation, China (ZR2018MC012, ZR2015HL099)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- PM2.5, prenatal exposure, vitamin B supplementation, autism-like behavior, folic acid, vitamin B6, vitamin B12, neuroinflammation, oxidative stress, mitochondrial damage, synaptic remodeling, neuronal apoptosis, neurogenesis, social communication deficits, spatial memory impairment, prenatal air pollution exposure, neuroprotection, inflammatory cytokines
- MeSH terms
- Air Pollutants, Animals, Autistic Disorder, Female, Hippocampus, Learning, Male, Mice, Inbred ICR, Pregnancy, Prenatal Exposure Delayed Effects, Synapses, Vitamin B Complex, Cytokines, Apoptosis, Dietary Supplements, Particulate Matter, Neurogenesis
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