MiR-130/SNAP-25 axis regulate presynaptic alteration in anterior cingulate cortex involved in lead induced attention deficits

Tao Wang, Rui Li Guan, Yun Feng Zou, Gang Zheng, Xue Feng Shen, Zi Peng Cao, Rui Hua Yang, Ming Chao Liu, Ke Jun Du, Xue Hang Li, Michael Aschner, Ming Gao Zhao, Jing Yuan Chen, Wen Jing Luo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number130249
JournalJournal of Hazardous Materials
Volume443
DOIs
StatePublished - Feb 5 2023

Keywords

  • Anterior cingulate cortex
  • Attention deficit
  • Lead (Pb)
  • Presynaptic function impairment

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution
  • Health, Toxicology and Mutagenesis

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