title: Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers.
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.
authors.affiliation: Center for Health Technologies, School of Life Sciences, Faculty of Science, University of Technology SydneyUltimo, NSW, Australia; Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of SydneyGlebe, NSW, Australia.
authors.forename: Yik Lung
authors.initials: YL
authors.lastname: Chan
authors.affiliation: Center for Health Technologies, School of Life Sciences, Faculty of Science, University of Technology SydneyUltimo, NSW, Australia; Renal Group Kolling Institute, Royal North Shore HospitalSt Leonards, NSW, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Saad
authors.affiliation: Center for Health Technologies, School of Life Sciences, Faculty of Science, University of Technology Sydney Ultimo, NSW, Australia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Odat
authors.affiliation: Center for Health Technologies, School of Life Sciences, Faculty of Science, University of Technology SydneyUltimo, NSW, Australia; Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of SydneyGlebe, NSW, Australia.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.affiliation: Renal Group Kolling Institute, Royal North Shore Hospital St Leonards, NSW, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Pollock
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales Kensington, NSW, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Jones
authors.affiliation: Center for Health Technologies, School of Life Sciences, Faculty of Science, University of Technology Sydney Ultimo, NSW, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
keywords: autophagy; gender difference; maternal smoking; mitophagy; oxidative stress