Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
J Hazard Mater. 2023 Feb 5;443(Pt B):130249. doi: 10.1016/j.jhazmat.2022.130249. Epub 2022 Oct 25.
Brain volume decrease in the anterior cingulate cortex (ACC) after lead (Pb) exposure has been linked to persistent impairment of attention behavior. However, the precise structural change and molecular mechanism for the Pb-induced ACC alteration and its contribution to inattention have yet to be fully characterized. The present study determined the role of miRNA regulated synaptic structural and functional impairment in the ACC and its relationship to attention deficit disorder in Pb exposed mice. Results showed that Pb exposure induced presynaptic impairment and structural alterations in the ACC. Furthermore, we screened for critical miRNA targets responsible for the synaptic alteration. We found that miR-130, which regulates presynaptic vesicle releasing protein SNAP-25, was responsible for the presynaptic impairment in the ACC and attention deficits in mice. Blocking miR-130 function reversed the Pb-induced decrease in the expression of its presynaptic target SNAP-25, leading to the redistribution of presynaptic vesicles, as well as improved presynaptic function and attention in Pb exposed mice. We report, for the first time, that miR-130 regulating SNAP-25 mediates Pb-induced presynaptic structural and functional impairment in the ACC along with attention deficit disorder in mice.
铅暴露后扣带回前部（ACC）脑体积减少与注意力行为持续受损有关。然而，铅诱导的 ACC 改变的确切结构变化和分子机制及其对注意力不集中的贡献仍有待充分阐明。本研究确定了 miRNA 调节的突触结构和功能损伤在 ACC 中的作用及其与铅暴露小鼠注意力缺陷障碍的关系。结果表明，铅暴露诱导 ACC 内的突触前损伤和结构改变。此外，我们筛选了负责突触改变的关键 miRNA 靶标。我们发现，调节突触小泡释放蛋白 SNAP-25 的 miR-130 负责 ACC 中的突触前损伤和小鼠的注意力缺陷。阻断 miR-130 的功能可逆转铅诱导的其突触前靶标 SNAP-25 表达减少，导致突触前囊泡重新分布，并改善铅暴露小鼠的突触前功能和注意力。我们首次报道，miR-130 调节 SNAP-25 介导了铅诱导的 ACC 内突触前结构和功能损伤以及小鼠的注意力缺陷障碍。
