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Effects of maternal smoking on brain development in offspring - Letter of Intent

Project Member(s): Chen, H.

Funding or Partner Organisation: US Department of Health and Human Services (National Institutes of Health (NIH))

Start year: 2014

Summary: Smoking and passive smoking during pregnancy are unfortunately still common throughout the world, despite established connections between cigarette smoke exposure (SE) and adverse health conditions in offspring. This project will address an important unknown in this field: the immediate and long-term effects of maternal smoking on fuel (glucose and amino acid) metabolism in the offspring brain and its contribution to increase susceptibility of ischemic-hypoxic brain injury. This project examines the effects of maternal smoking on offspring brain fuel metabolism. Its central hypothesis is that intrauterine cigarette smoke exposure can impair fetal neural glucose and amino acid transportation and metabolism, rendering offspring more susceptible to severe tissue damage in ischemic situations. This vulnerability could have immediate and lifelong implications, as birth complications are higher in mothers who smoke, with an increased chance of ischemic-hypoxia injury occurring during the birth process. The proposed mechanisms underlying the vulnerability are: 1) changes in fuel transporters and metabolic enzymes; and 2) mitochondrial dysfunction due to DNA methylation and DNA damage. Markers of brain glucose and amino acid metabolism, as well as mitochondrial biogenesis, oxidative stress, DNA methylation and damage, and neuron apoptosis will all be measured in offspring brain tissues at different ages, in addition to behavioral outcomes, under both normal and ischemic-hypoxia injury conditions.

Keywords: maternal smoking, hypoxia-ischemic injury, mouse

FOR Codes: Animal Physiology - Systems, Behaviour and Health