Cobalt accumulation and iron-regulatory protein profile expression in immature mouse brain after perinatal exposure to cobalt chloride

Chem Biol Interact. 2020 Sep 25:329:109217. doi: 10.1016/j.cbi.2020.109217. Epub 2020 Aug 1.

Abstract

Developing brain is very sensitive to the influence of environmental factors during gestation and the neonatal period. The aim of the study is to assess cobalt and iron accumulation in the brain as well as changes in the expression of iron-regulatory proteins transferrin receptor 1, hepcidin, and ferroportin in suckling mice. Perinatal exposure to cobalt chloride increased significantly cobalt content in brain tissue homogenates of 18-day-old (d18) and 25-day-old (d25) mice inducing alterations in brain iron homeostasis. Higher degree of transferrin receptor 1 expression was demonstrated in cobalt chloride-exposed mice with no substantial changes between d18 and d25 mice. A weak ferroportin expression was found in 18-day-old control and cobalt-treated mouse brain. Cobalt exposure of d25 mice resulted in increased ferroportin expression in brain compared to the untreated age-matched control group. Hepcidin level in cobalt-exposed groups was decreased in d18 mice and slightly increased in d25 mice. The obtained data contribute for the better understanding of metal toxicity impact on iron homeostasis in the developing brain with further possible implications in neurodegeneration.

Keywords: Cobalt; Ferroportin; Hepcidin; Immature brain; Iron; Transferrin receptor 1.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cobalt / metabolism
  • Cobalt / pharmacology*
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Hepcidins / genetics
  • Hepcidins / metabolism
  • Iron / metabolism
  • Iron-Regulatory Proteins / genetics
  • Iron-Regulatory Proteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / metabolism

Substances

  • Cation Transport Proteins
  • Hepcidins
  • Iron-Regulatory Proteins
  • Receptors, Transferrin
  • Tfrc protein, mouse
  • metal transporting protein 1
  • Cobalt
  • Iron
  • cobaltous chloride