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Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
Department of Anatomy and Cell Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 1 April 2013; in revised form: 3 June 2013 / Accepted: 4 June 2013 / Published: 19 June 2013
Abstract: Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.
Keywords: fetal alcohol syndrome; fetal alcohol spectrum disorder; ethanol; central nervous system; cranial neural crest cells; vitamin deficiency
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Muralidharan, P.; Sarmah, S.; Zhou, F.C.; Marrs, J.A. Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets. Brain Sci. 2013, 3, 964-991.
Muralidharan P, Sarmah S, Zhou FC, Marrs JA. Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets. Brain Sciences. 2013; 3(2):964-991.
Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A. 2013. "Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets." Brain Sci. 3, no. 2: 964-991.