Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 23, pp 2859–2870

Ethanol impairs Rho GTPase signaling and differentiation of cerebellar granule neurons in a rodent model of fetal alcohol syndrome

  • S. Joshi
  • R. S. Guleria
  • J. Pan
  • K. J. Bayless
  • G. E. Davis
  • D. DiPette
  • U. S. Singh
Research Article

DOI: 10.1007/s00018-006-6333-y

Cite this article as:
Joshi, S., Guleria, R.S., Pan, J. et al. Cell. Mol. Life Sci. (2006) 63: 2859. doi:10.1007/s00018-006-6333-y
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Abstract.

Developmental exposure to ethanol impairs fetal brain development and causes fetal alcohol syndrome. Although the cerebellum is one of the most alcohol-sensitive brain areas, signaling mechanisms underlying the deleterious effects of ethanol on developing cerebellar granule neurons (CGNs) are largely unknown. Here we describe the effects of in vivo ethanol exposure on neurite formation in CGNs and on the activation of Rho GTPases (RhoA and Rac1), regulators of neurite formation. Exposure of 7-day-old rat pups to ethanol for 3 h moderately increased blood alcohol concentration (BAC) (∼40 mM) and inhibited neurite formation and Rac1 activation in CGNs. Longer exposure to ethanol for 5 h resulted in higher BAC (∼80 mM), induced apoptosis, inhibited Rac1, and activated RhoA. Studies demonstrated a regulatory role of Rho GTPases in differentiation of cerebellar neurons, and indicated that ethanol-associated impairment of Rho GTPase signaling might contribute to brain defects observed in fetal alcohol syndrome.

Keywords.

Cerebellar granular neuronsRhoARac1fetal alcohol syndromeneuronal differentiation

Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • S. Joshi
    • 1
    • 2
  • R. S. Guleria
    • 1
    • 2
  • J. Pan
    • 1
    • 2
  • K. J. Bayless
    • 3
  • G. E. Davis
    • 3
  • D. DiPette
    • 1
    • 2
  • U. S. Singh
    • 1
    • 2
  1. 1.Department of Internal Medicine, Division of Molecular Cardiology, Cardiovascular Research and Cancer InstituteThe Texas A & M University System Health Science Center, College of MedicineCollege StationUSA
  2. 2.Scott & White; Central Texas Veterans Health Care SystemTempleUSA
  3. 3.Department of Pathology and Laboratory MedicineThe Texas A & M University System Health Science CenterCollege StationUSA