Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta

Details

• Personal Author:
  Bower KA ; Chen G ; Ding M ; Ke ZJ ; Luo J ; Shi XL ; Xu M
• Description:
  Ethanol is a potent teratogen for the developing central nervous system (CNS), and fetal alcohol syndrome (FAS) is the most common nonhereditary cause of mental retardation. Ethanol disrupts neuronal differentiation and maturation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Using an in vitro neuronal model, mouse Neuro2a (N2a) neuroblastoma cells, we demonstrated that ethanol inhibited neurite outgrowth and the expression of neurofilament (NF) proteins. Glycogen synthase kinase 3 beta (GSK3 beta), a multifunctional serine/threonine kinase negatively regulated neurite outgrowth of N2a cells; inhibiting GSK3 beta activity by retinoic acid (RA) and lithium induced neurite outgrowth, while over-expression of a constitutively active S9A GSK3 beta mutant prevented neurite outgrowth. Ethanol inhibited neurite outgrowth by activating GSK3 beta through the dephosphorylation of GSK3 beta at serine 9. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family rich in many edible berries and other pigmented fruits, enhanced neurite outgrowth by promoting p-GSK3 beta(Ser9). More importantly, C3G reversed ethanol-mediated activation of GSK3 beta and inhibition of neurite outgrowth as well as the expression of NF proteins. C3G also blocked ethanol-induced intracellular accumulation of reactive oxygen species (ROS). However, the antioxidant effect of C3G appeared minimally involved in its protection. Our study provides a potential avenue for preventing or ameliorating ethanol-induced damage to the developing CNS. [Description provided by NIOSH]
• Subjects:
  Chemistry Hypersensitivity Laboratories Mental Disorders Mental Health Nervous System Occupational Health Safety
• Keywords:
  Author Keywords: Alcohol Cell-biology Cell-metabolism Cellular-reactions Central-nervous-system Chemical-hypersensitivity Chemical-reactions Development Differentiation Fetal Alcohol Syndrome Laboratory-animals Mental-disorders Mental-illness Neuroprotection Neurotoxic-effects

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• ISSN:
  1029-8428
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  321-331
• Volume:
  15
• Issue:
  4
• NIOSHTIC Number:
  nn:20035324
• Citation:
  Neurotox Res 2009 May; 15(4):321-331
• Contact Point Address:
  Jia Luo, University of Kentucky, Department of Internal Medicine, College of Medicine, 124C Combs Res Bldg,800 Rose St, Lexington, KY 40536
• Email:
  jialuo888@uky.edu
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  True
• Source Full Name:
  Neurotoxicity Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0a4a21b3f81a04d9b5d4244bba2ca107872f58e595b2e2687c130fc5ed693252104daef950a56299c34aaed01788167eb00cf7241a2417b61771340e782dade1
• Download URL:
  https://stacks.cdc.gov/view/cdc/187229/cdc_187229_DS1.pdf
• File Type:
  [PDF - 578.64 KB ]