Abstract

Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring. Female Balb/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation and lactation with or without L-Carnitine supplementation (1.5 mM in drinking water). In 1 day old male SE offspring, brain mitochondrial damage was suggested by increased mitochondrial fusion and reduced autophagosome markers; whereas at 13 weeks, enhanced brain cell damage was suggested by reduced fission and autophagosome markers, as well as increased apoptosis and DNA fragmentation markers, which were partially reversed by maternal L-Carnitine supplementation. In female SE offspring, enhanced mitochondrial regeneration was suggested by decreased fission and increased fusion markers at day 1. At 13 weeks, there was an increase in brain energy demand, oxidative stress and mitochondrial turnover, reflected by the protein changes of OXPHOS complex, fission and autophagosome markers, as well as the endogenous antioxidant, which were also partially normalized by maternal L-Carnitine supplementation. However, markers of apoptosis and DNA fragmentation were not significantly changed. Thus L-Carnitine supplementation may benefit the brain health of the offspring from smoking mothers.

Highlights

  • Cigarette smoking is a leading cause of death and morbidity worldwide

  • Mitophagy Markers At P1, mitochondrial dynamin-related protein-1 (Drp-1) was increased by 50% in smoke exposed (SE) offspring compared to sham exposure (SHAM) (P < 0.05, Figure 1A); while fission protein (Fis-1), phosphatase and tensin homolog induced putative kinase (Pink-1), and Parkin and optic atrophy 1 (Opa-1) levels were similar between the SHAM and SE offspring (Figures 1D,G,J,M)

  • At 13 weeks, brain mitochondrial levels of dynamin-related protein (Drp)-1, fission protein (Fis)-1, and optic atrophy (Opa)-1 were decreased in the SE offspring (P < 0.05, Figures 1C,F,O)

Read more

Summary

Introduction

Cigarette smoking is a leading cause of death and morbidity worldwide. Despite increased public education and government policies to ban smoking in public places (Balmford et al, 2016), smoking among women of childbearing age and during pregnancy is still common (Mendelsohn et al, 2014). Mitophagy is when autophagy occurs in the mitochondria, which is an important quality control mechanism to remove damaged mitochondria (Ashrafi and Schwarz, 2013) This process recycles intact mitochondrial fragments to generate new healthy mitochondria through fission and fusion (Bereiter-Hahn, 1990; Westermann, 2010) to maintain mitochondrial integrity. Our previous data suggests that maternal SE impairs brain mitochondrial levels of oxidative phosphorylation (OXPHOS) complexes in male offspring with reduced endogenous antioxidant capacity from birth (Chan et al, 2016b). This is due to the changes of mitochondrial dynamics in the brain from birth to adulthood (Hagberg et al, 2014).

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call