ZFIN ID: ZDB-PUB-140819-2
Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish — Implication in neural tube defects and Alzheimer's diseases
Kao, T.T., Chu, C.Y., Lee, G.H., Hsiao, T.H., Cheng, N.W., Chang, N.S., Chen, B.H., Fu, T.F.
Date: 2014
Source: Neurobiology of disease 71: 234-44 (Journal)
Registered Authors:
Keywords: Alzheimer’s diseases, folate deficiency, neural tube defects, one-carbon metabolism, zebrafish, γ–glutamyl hydrolase
MeSH Terms:
  • Acetylcysteine/metabolism
  • Acetylcysteine/pharmacology
  • Aging/genetics*
  • Alzheimer Disease/etiology*
  • Alzheimer Disease/genetics
  • Animals
  • Animals, Genetically Modified
  • Cathepsin B/genetics
  • Cathepsin B/metabolism
  • Cell Movement/genetics
  • Embryo, Nonmammalian
  • Folic Acid/metabolism
  • Folic Acid Deficiency*/complications
  • Folic Acid Deficiency*/genetics
  • Folic Acid Deficiency*/pathology
  • Green Fluorescent Proteins/genetics
  • Hot Temperature/adverse effects
  • Microtubule-Associated Proteins/metabolism
  • Neural Crest/physiology
  • Neural Tube Defects/etiology*
  • Neural Tube Defects/genetics
  • Oxidative Stress/drug effects
  • Oxidative Stress/genetics*
  • Time Factors
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • gamma-Glutamyl Hydrolase/metabolism
PubMed: 25131448 Full text @ Neurobiol. Dis.
Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.