PMID- 29164515 OWN - NLM STAT- MEDLINE DCOM- 20181022 LR - 20181022 IS - 1559-0720 (Electronic) IS - 0163-4984 (Linking) VI - 184 IP - 2 DP - 2018 Aug TI - Early-Life Exposure to Cadmium Triggers Distinct Zn-Dependent Protein Expression Patterns and Impairs Brain Development. PG - 409-421 LID - 10.1007/s12011-017-1201-1 [doi] AB - 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-kappaB, 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. FAU - Mimouna, Safa Ben AU - Mimouna SB AD - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut de Biotechnologie, Universite de Monastir, 5000, Monastir, Tunisia. FAU - Chemek, Marouane AU - Chemek M AD - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut de Biotechnologie, Universite de Monastir, 5000, Monastir, Tunisia. FAU - Boughammoura, Sana AU - Boughammoura S AD - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut de Biotechnologie, Universite de Monastir, 5000, Monastir, Tunisia. FAU - Banni, Mohamed AU - Banni M AD - Laboratoire de Biochimie et Toxicologie Environnementale, ISA, Chott-Mariem, 4042, Sousse, Tunisia. FAU - Messaoudi, Imed AU - Messaoudi I AUID- ORCID: 0000-0002-4025-8765 AD - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut de Biotechnologie, Universite de Monastir, 5000, Monastir, Tunisia. imed_messaoudi@yahoo.fr. AD - Institut de Biotechnologie, Imed MESSAOUDI, 5000, Monastir, Tunisia. imed_messaoudi@yahoo.fr. LA - eng PT - Journal Article DEP - 20171122 PL - United States TA - Biol Trace Elem Res JT - Biological trace element research JID - 7911509 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cation Transport Proteins) RN - 0 (zinc transporter 3, rat) RN - 00BH33GNGH (Cadmium) RN - 9038-94-2 (Metallothionein) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - J41CSQ7QDS (Zinc) SB - IM MH - Animals MH - Brain/*drug effects/growth & development/metabolism MH - Brain-Derived Neurotrophic Factor/genetics MH - Cadmium/administration & dosage/metabolism/*pharmacology MH - Cation Transport Proteins/genetics MH - Female MH - Gene Expression Regulation, Developmental/*drug effects MH - Male MH - Metallothionein/metabolism MH - Organ Size/drug effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*genetics/metabolism MH - Rats, Wistar MH - Superoxide Dismutase/metabolism MH - Zinc/administration & dosage/metabolism/*pharmacology OTO - NOTNLM OT - Brain development OT - Cadmium OT - Rat OT - Zinc OT - Zn-dependent proteins EDAT- 2017/11/23 06:00 MHDA- 2018/10/23 06:00 CRDT- 2017/11/23 06:00 PHST- 2017/09/26 00:00 [received] PHST- 2017/11/07 00:00 [accepted] PHST- 2017/11/23 06:00 [pubmed] PHST- 2018/10/23 06:00 [medline] PHST- 2017/11/23 06:00 [entrez] AID - 10.1007/s12011-017-1201-1 [pii] AID - 10.1007/s12011-017-1201-1 [doi] PST - ppublish SO - Biol Trace Elem Res. 2018 Aug;184(2):409-421. doi: 10.1007/s12011-017-1201-1. Epub 2017 Nov 22.