Protection against Prenatal Alcohol-Induced Damage

F etal alcohol syndrome (FAS) is the most common, nongenetic cause of mental retardation, and has a signifi cant national health impact [1]. Meeting the criteria for this condition requires the identifi cation of specifi c features, involving craniofacial dysmorphology (particularly midfacial anomalies), growth retardation, and defi cits in brain function. Most children with alcohol-induced prenatal defi cits do not have this full syndrome, but, instead, they fall under the umbrella term of fetal alcohol spectrum disorder (FASD). These disorders result from prenatal alcohol exposure, and the sequelae include specifi c neurodevelopmental and behavioral disorders. Recent reports suggest that fetal alcohol spectrum disorders affect one out of 100 children born in the United States [2]. There have been numerous public health approaches to alerting women to the dangers of drinking during pregnancy—including warning labels appearing on alcoholic beverages in 1989 (Box 1), and a US Surgeon General warning issued in 1981 (updated and reissued in 2005) urging women who are pregnant or who may become pregnant to abstain from alcohol (http:⁄⁄www.hhs. gov/surgeongeneral/pressreleases/ sg02222005.html). Yet despite these warnings, alcohol use during pregnancy is common, with up to 50% of women of childbearing age consuming alcohol, 15%–20% acknowledging continuing to drink when pregnant, and one in 25 pregnant women reporting binge drinking [3,4]. It is critically important to understand the role of alcohol's effects during pregnancy for two main reasons. First, such knowledge will help to bolster public health warnings about drinking during pregnancy. Second, a better understanding of how alcohol causes fetal damage will help in developing preventive interventions to protect the fetus in situations where it is exposed to alcohol. Researchers have evaluated a number of therapies for the prevention of alcohol-induced damage in model systems. These therapies include neuroprotective peptides [5–7] and antioxidants targeting the prevention of ethanol-induced apoptosis [8,9]. And now Ieraci and Herrera report in PLoS Medicine that nicotinamide, a drug that has been used in humans to treat autoimmune diseases such as diabetes and bullous pemphigoid, protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain [10]. Their study provides a substantial contribution toward fi nding a treatment to prevent alcohol-induced damage. Ieraci and Herrera treated seven-day-old mice with 20% ethanol. The animals were also treated with nicotinamide at varying doses and time points; in each litter, animals were equally distributed into the different treatment groups. Cytochrome-c release (which is released from mitochondria during oxygen–glucose deprivation) …