Regeneration, Repair, and Developmental NeuroscienceResearch PaperA maternal diet supplemented with creatine from mid-pregnancy protects the newborn spiny mouse brain from birth hypoxia
Highlights
▶We model birth hypoxia using the precocial spiny mouse. ▶Hypoxia significantly increased lipid peroxidation in the cerebrum. ▶Hypoxia caused region-dependent increases in BAX, cytochrome c and caspase-3. ▶Maternal creatine supplementation prevented adverse changes in hypoxia brains. ▶Creatine has neuroprotective capacity for newborn.
Section snippets
Animals
All experiments were approved in advance by Monash University School of Biomedical Sciences Animal Ethics Committee, and conducted according to the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. The spiny mice used in this study were obtained from our own laboratory colony and housed, bred and time-mated as previously described (Dickinson and Walker, 2007).
Diet
Pregnant dams were fed either a control diet of standard rat and mouse pellets throughout pregnancy,
Lipid peroxidation in the brain
At 24 h of age lipid peroxidation (as measured by MDA) was significantly increased in the cerebrum of pups in the birth hypoxia group compared to all other groups (P≤0.05; Fig. 1). No such increase was observed in the birth hypoxia pups whose mothers had received the creatine supplemented diet from day 20 of pregnancy.
Activation of the apoptotic cell death pathway in the brain
Birth hypoxia induced a significant increase in the expression of the pro-apoptotic protein BAX in the cortical subplate and the thalamus (P<0.05; Fig. 2A, C), and a strong trend
Discussion
This study investigated the potential for maternal creatine supplementation from mid-pregnancy to reduce hypoxia-induced lipid peroxidation, maintain intra-mitochondrial stores of cytochrome-c, and prevent activation of the apoptotic pathway in the newborn brain following birth hypoxia. In pups subjected to intrapartum hypoxia, at 24 h after birth we observed an increase in lipid peroxidation, and region-specific increases in cytoplasmic cytochrome c, and increased expression of the
Conclusions
This study shows that maternal dietary creatine supplementation throughout the second half of pregnancy significantly protects fetal cortical and deep gray matter from injury arising from intrapartum hypoxia. It is yet to be shown whether creatine provides neuroprotection beyond the immediate postnatal period, and further investigation into the long-term brain development of these offspring is warranted, with particular reference to cognitive and motor development. It is appropriate that
Acknowledgments
We thank Dr. Lisa Hutton for assistance with immunohistochemical protocols. This project was supported by grants from the National Health & Medical Research Council of Australia to DWW, MCM and RS.
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Present address of Z. Ireland: Queensland Cerebral Palsy & Rehabilitation Research Centre, Royal Children's Hospital, Herston, QLD, Australia, 4029.