Lead-induced neurodevelopmental lesion and epigenetic landscape: Implication in neurological disorders

J Appl Toxicol. 2023 Sep;43(9):1256-1271. doi: 10.1002/jat.4419. Epub 2022 Dec 13.

Abstract

Lead (Pb) was implicated in multiple genotoxic, neuroepigenotoxic, and chromosomal-toxic mechanisms and interacted with varying synaptic plasticity pathways, likely underpinning previous reports of links between Pb and cognitive impairment. Epigenetic changes have emerged as a promising biomarker for neurological disorders, including cognitive disorders, Alzheimer's disease (AD), and Parkinson's disease (PD). In the present review, special attention is paid to neural epigenetic features and mechanisms that can alter gene expression patterns upon environmental Pb exposure in rodents, primates, and zebrafish. Epigenetic modifications have also been discussed in population studies and cell experiment. Further, we explore growing evidence of potential linkage between Pb-induced disruption of regulatory pathway and neurodevelopmental and neurological disorders both in vivo and in vitro. These findings uncover how epigenome in neurons facilitates the development and function of the brain in response to Pb insult.

Keywords: epigenetic; lead; neurodevelopment; neurological disorders; toxicosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Animals
  • Epigenesis, Genetic
  • Lead / toxicity
  • Nervous System Diseases* / chemically induced
  • Nervous System Diseases* / genetics
  • Zebrafish

Substances

  • Lead