Cadmium-induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum

J Biochem Mol Toxicol. 2019 Apr;33(4):e22274. doi: 10.1002/jbt.22274. Epub 2018 Dec 1.

Abstract

Background: Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development.

Objectives: This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes.

Methods: Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay.

Results: A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium-treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium-treated rats.

Keywords: Nkx2.2; Pax6; cadmium; cerebellum; neurodegeneration; sonic hedgehog.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cadmium / toxicity*
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Cerebellum / pathology
  • DNA Damage
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Homeobox Protein Nkx-2.2
  • Immunohistochemistry
  • Male
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Motor Activity / drug effects
  • Oxidative Stress / drug effects
  • Polymerase Chain Reaction
  • Rats, Wistar
  • Signal Transduction / drug effects*

Substances

  • Hedgehog Proteins
  • Homeobox Protein Nkx-2.2
  • Nkx2-2 protein, rat
  • Shh protein, rat
  • Cadmium