Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring

Sci Rep. 2016 May 12:6:25881. doi: 10.1038/srep25881.

Abstract

Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring's brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1α and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1α was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cytokines / genetics
  • Encephalitis / chemically induced*
  • Encephalitis / genetics
  • Encephalitis / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Male
  • Maternal Exposure / adverse effects*
  • Mice
  • Mice, Inbred BALB C
  • Nicotiana / adverse effects*
  • Oxidative Stress
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / metabolism
  • Smoke / adverse effects*
  • Toll-Like Receptor 4 / genetics
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Smoke
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • 3-nitrotyrosine
  • Tyrosine