Neuronal Cell Migration in Fetal Alcohol Syndrome

  • Tatsuro Kumada
  • Yutaro Komuro
  • Ying Li
  • Yoav Littner
  • Hitoshi Komuro


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 produces severe alcohol-induced damage in the developing brain. FAS children experience ataxia, deficits in intellectual functioning, difficulties in learning, memory, problem-solving, and attention. Multiple aspects of central nervous system development can be affected by alcohol exposure, but the most striking abnormalities are in neuronal cell migration. Although the cellular mechanisms by which alcohol affects the migration of immature neurons are not fully understood, recent studies reveal that Ca2+ signaling and cyclic nucleotide signaling are the central targets of alcohol action in neuronal cell migration. An acute administration of ethanol reduces the frequency of transient Ca2+ elevations in migrating neurons and cGMP levels, and increases cAMP levels. Experimental manipulations of these second messenger pathways, through stimulating Ca2+ and cGMP signaling or inhibiting cAMP signaling, completely reverses the action of ethanol on neuronal cell migration in vitro as well as in vivo. Each second-messenger has multiple but distinct downstream targets, including CaMKII, calcineurin, PP1, Rho GTPase, MAPK, and PI3K. Therefore, the aberrant migration of immature neurons in the fetal brain caused by maternal alcohol consumption may be corrected by controlling the activity of these second-messenger pathways. In this chapter, using cerebellar granule cell migration as a model system, we first describe how alcohol exposure impairs the migration of immature neurons, and then discuss the signaling mechanisms involved.


Granule Cell Alcohol Exposure Cerebellar Granule Cell Fetal Alcohol Spectrum Disorder Fetal Alcohol Spectrum Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Fetal alcohol syndrome


Fetal alcohol spectrum disorders


External granular layer


Molecular layer


Purkinje cell layer


Internal granular layer


White matter




Cyclic AMP


Cyclic GMP


Adenylyl cyclase


Protein kinase A


Cyclic nucleotide phosphodiesterases


Protein kinase C


Ca2+/calmodulin-dependent protein kinase II


Protein phosphatase 1


Mitogen-activated protein kinase


Phosphoinositide 3-kinase





This work was supported by a grant (AA 13613) from National Institute on Alcohol Abuse and Alcoholism and a grant (R01 ES015612) from National Institute of Environmental Health Sciences.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Tatsuro Kumada
  • Yutaro Komuro
  • Ying Li
  • Yoav Littner
  • Hitoshi Komuro
    • 1
  1. 1.Department of Neurosciences/NC30, Lerner Research InstituteThe Cleveland Clinic FoundationClevelandUSA

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