title: Alcohol teratogenesis: mechanisms of damage and strategies for intervention.
abstract: There are multiple mechanisms by which alcohol can damage the developing brain, but the type of damage induced will depend on the amount and developmental timing of exposure, along with other maternal and genetic factors. This article reviews current perspectives on how ethanol can produce neuroteratogenic effects by its interactions with molecular regulators of brain development. The current evidence suggests that alcohol produces many of its damaging effects by exerting specific actions on molecules that regulate key developmental processes (e.g., L1 cell adhesion molecule, alcohol dehydrogenase, catalase), interfering with the early development of midline serotonergic neurons and disrupting their regulatory-signaling function for other target brain structures, interfering with trophic factors that regulate neurogenesis and cell survival, or inducing excessive cell death via oxidative stress or activation of caspase-3 proteases. The current understanding of pathogenesis mechanisms suggests several strategic approaches to develop rational molecular prevention. However, the development of behavioral and biologic treatments for alcohol-affected children is crucial because it is unlikely that effective delivery of preventative interventions can realistically be achieved in ways to prevent prenatal damage in at-risk pregnancies. Toward that end, behavioral training that promotes experience-dependent neuroplasticity has been effective in a rat model of cerebellar damage induced by alcohol exposure during the period of brain development that is comparable to that of the human third trimester.
authors.affiliation: Department of Psychology, Indiana University-Purdue University at Indianapolis, 402 North Blackford Street, Indianapolis, Indiana 46202, USA. goodlett@iupui.edu
authors.forename: Charles R
authors.initials: CR
authors.lastname: Goodlett
authors.forename: Kristin H
authors.initials: KH
authors.lastname: Horn
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001925:Brain Damage, Chronic / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D006801:Humans; D009473:Neuronal Plasticity; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D058825:Serotonin 5-HT1 Receptor Agonists; D013723:Teratogens / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D013723:Teratogens; D000431:Ethanol