Pb exposure reduces the expression of SNX6 and Homer1 in offspring rats and PC12 cells

Toxicology. 2019 Mar 15:416:23-29. doi: 10.1016/j.tox.2019.02.002. Epub 2019 Feb 6.

Abstract

Lead (Pb) is a widespread environmental heavy metal toxicant and chronic Pb exposure can have irreversible effects on memory and cognitive function, which is closely related to dendritic spines. Studies have shown that SNX6 and Homer1 can regulate the growth of dendritic spines. We aimed to investigate the effect of Pb exposure on the dendritic spines in hippocampus, the expression of SNX6 and Homer1 in rats and PC12 cells. The animals were randomly divided to three groups: control group, low lead group and high lead group. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM Pb acetate. The results showed that the Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group. The morphology of dendritic spines in hippocampus after Pb treatment was changed and the density of dendritic spines was reduced. The expression of SNX6 and Homer1 was decreased in Pb exposed groups compared with the control group. Furthermore, up-regulation of SNX6 expression could reverse the down-regulation of Pb exposure on Homer1. These results indicate that Pb exposure can reduce the expression of SNX6 and lead to a decrease in Homer1 expression, which affects the changes in dendritic spines causing learning and memory impairment.

Keywords: Dendritic spine; Homer1; Lead (Pb); Sorting nexin 6 (SNX6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Down-Regulation
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Homer Scaffolding Proteins / genetics
  • Homer Scaffolding Proteins / metabolism*
  • Lead Poisoning, Nervous System / etiology*
  • Lead Poisoning, Nervous System / genetics
  • Lead Poisoning, Nervous System / metabolism
  • Lead Poisoning, Nervous System / pathology
  • Male
  • Organometallic Compounds / toxicity*
  • PC12 Cells
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism*

Substances

  • Homer Scaffolding Proteins
  • Homer1 protein, rat
  • Organometallic Compounds
  • Snx6 protein, rat
  • Sorting Nexins
  • lead acetate