Biological Trace Element Research

, Volume 184, Issue 2, pp 409–421 | Cite as

Early-Life Exposure to Cadmium Triggers Distinct Zn-Dependent Protein Expression Patterns and Impairs Brain Development

  • Safa Ben Mimouna
  • Marouane Chemek
  • Sana Boughammoura
  • Mohamed Banni
  • Imed MessaoudiEmail author


The objective of this study was to determine if the brain development impairment induced by early-life exposure to cadmium (Cd) could result from changes in the expression pattern of distinct zinc (Zn)-dependent proteins. For this purpose, adult female rats receiving either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation and lactation periods were used. After birth, the male offspring were screened for locomotors and sensorial defects. At postnatal day 21 (PND 21), the male pups were sacrificed and their brains, liver, and plasma were taken for chemical, biochemical, and molecular analyses. Our results show that exposure to Cd significantly increased the metal accumulation and decreased Zn concentrations in the brain of male pups from Cd-treated mothers. Besides, Cd exposure reduced significantly the locomotor activity of the offspring in open-field test, the body weight, and the cranio-caudal length at PND21. Insulin-like growth factor-I (IGF-1) levels in the plasma and liver were also decreased in male pups from Cd-treated mothers. Cd-induced brain development disruption was accompanied by a significant increase of the superoxide dismutase (SOD) activity, induction of the metallothionein (MT) synthesis, and, at the molecular level, by an upregulation of Zrt-,Irt-related protein 6 (ZIP6) gene and a significant downregulation of the expression of the Zn transporter 3 (ZnT3) and brain-derived neurotrophic factor (BDNF) genes in the brain. No significant changes on the expression of genes encoding other Zn-dependent proteins and factors such as ZnT1, ZIP12, NF-κB, and Zif268. Interestingly, Zn supplementation provided a total or partial correction of the changes induced by the Cd exposure. These data indicated that changes in expression of ZnT3 and ZIP6 as well as alteration of other transcription factors, such as BDNF, or Zn-dependent proteins, such as SOD and MTs, in response to Cd exposure might be an underlying mechanism of Cd-induced brain development impairment.


Brain development Cadmium Rat Zinc Zn-dependent proteins 



This research was supported by the Ministry of Higher Education, Scientific Research and Technology of Tunisia.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there are no conflicts of interest.


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Authors and Affiliations

  1. 1.LR11ES41: Génétique, Biodiversité et Valorisation des Bioressources, Institut de BiotechnologieUniversité de MonastirMonastirTunisia
  2. 2.Laboratoire de Biochimie et Toxicologie EnvironnementaleISASousseTunisia
  3. 3.Institut de BiotechnologieImed MESSAOUDIMonastirTunisia

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