Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish - Implication in neural tube defects and Alzheimer's diseases

Tseng Ting Kao, Chia Yi Chu, Gang Hui Lee, Tsun Hsien Hsiao, Nai Wei Cheng, Nan Shan Chang, Bing Hung Chen, Tzu Fun Fu

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalNeurobiology of Disease
Volume71
Issue number1
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Neurology

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