Maternal alcohol consumption during pregnancy can cause serious birth defects, of which fetal alcohol syndrome (FAS) is the most devastating. Recognized by characteristic craniofacial abnormalities and growth deficiency, this condition includes severe alcohol-induced damage to the developing brain. FAS children experience deficits in intellectual functioning; difficulties in learning, memory, problem solving, and attention; difficulties with mental health and social interactions. The long-term goal of present proposal is to elucidate the cellular and molecular mechanisms underlying alcohol-induced malformation of brain. Specially, we will focus on the effects of alcohol on neuronal cell migration in the developing brain, since many ectopic neurons are found in the brain of FAS patients, suggesting that alcohol exposure causes abnormal migration of immature neurons. To this end, we use cerebellum as a model system, because the effect of alcohol on brain growth is especially marked in the cerebellum. We will determine the effects of alcohol on the cerebellar granule cell migration. First, we will determine when, where and how alcohol alters the migration of cerebellar granule cells in a real-time manner with the use of acute cerebellar slice preparations and microexplant cultures. In particularly, we will examine a relationship between mounts and durations of alcohol administration and inhibition of cell movement. Second, we will determine whether changes in intracellular Ca2+ fluctuations and membrane potential of migrating granule cells are involved in alcohol-induced alteration of neuronal migration. Third, we will determine whether manipulations of intracellular Ca2+ fluctuations and membrane potentials by activating NMDA receptor or inhibiting K+ channel activity can overcome the alcohol-induced changes in cell migration. The fundamental mechanisms whereby ethanol administration leads to the disturbances of brain development have not been delineated definitively. Answers to the questions raised in this project will provide a new insight for understanding how prenatal and early postnatal exposure to alcohol causes malformation of brain.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Foudin, Laurie L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
Zip Code
Moorman, Sara M; Carr, Deborah; Kirchhoff, Karin T et al. (2012) An assessment of social diffusion in the Respecting Choices advance care planning program. Death Stud 36:301-22
Moorman, Sara M (2011) Older adults' preferences for independent or delegated end-of-life medical decision making. J Aging Health 23:135-57
Moorman, Sara M (2011) The Importance of Feeling Understood in Marital Conversations about End-of-Life Health Care. J Soc Pers Relat 28:100-116
Jiang, Yulan; Kumada, Tatsuro; Cameron, D Bryant et al. (2008) Cerebellar granule cell migration and the effects of alcohol. Dev Neurosci 30:7-23
Cameron, D B; Galas, L; Jiang, Y et al. (2007) Cerebellar cortical-layer-specific control of neuronal migration by pituitary adenylate cyclase-activating polypeptide. Neuroscience 146:697-712
Kumada, Tatsuro; Jiang, Yulan; Cameron, D Bryant et al. (2007) How does alcohol impair neuronal migration? J Neurosci Res 85:465-70
Kumada, Tatsuro; Lakshmana, Madepalli K; Komuro, Hitoshi (2006) Reversal of neuronal migration in a mouse model of fetal alcohol syndrome by controlling second-messenger signalings. J Neurosci 26:742-56
Komuro, Hitoshi; Kumada, Tatsuro (2005) Ca2+ transients control CNS neuronal migration. Cell Calcium 37:387-93
Kumada, Tatsuro; Komuro, Hitoshi (2004) Completion of neuronal migration regulated by loss of Ca(2+) transients. Proc Natl Acad Sci U S A 101:8479-84