Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system.

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  • Additional Information
    • Source:
      Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print Cited Medium: Print ISSN: 0022-3042 (Print) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
      Original Publication: New York : Raven Press
    • Subject Terms:
      1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology ; Dopamine/*metabolism ; Glutathione/*physiology ; Nerve Tissue Proteins/*pharmacology ; Neurons/*drug effects ; Oxidopamine/*pharmacology; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/antagonists & inhibitors ; Animals ; Brain-Derived Neurotrophic Factor ; Glutathione/analogs & derivatives ; Glutathione/antagonists & inhibitors ; Glutathione Disulfide ; Immunohistochemistry ; Nerve Growth Factors/pharmacology ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Neurons/metabolism ; Oxidopamine/antagonists & inhibitors ; Tumor Cells, Cultured
    • Abstract:
      Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the survival of dopamine neurons in cultures derived from the embryonic rat mesencephalon. We now extend this study by demonstrating that, in addition to the effect of sustaining survival of dopaminergic neurons, BDNF also confers protection against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenylpyridinium ion (MPP+). Exposure of mesencephalic cultures to either 6-OHDA or MPP+ resulted in a loss of 70-80% of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunocytochemistry. In BDNF-treated cultures, loss of TH-positive cells after exposure to either toxin was reduced to only 30%. To facilitate biochemical measurements, we studied SH-SY5Y dopaminergic neuroblastoma cells. BDNF was found to protect these cells from the dopaminergic neurotoxins, 6-OHDA and MPP+. Indicative of oxidative stress, treatment of SH-SY5Y cells with 10 microM 6-OHDA for 24 h caused a fivefold increase in the levels of oxidized glutathione (GSSG). Pretreatment with BDNF for 24 h completely prevented the rise in GSSG. Further examination revealed that BDNF increased the activity of the protective enzyme, glutathione reductase, by 100%. In contrast, BDNF had no effect on the activity of catalase. These results add further impetus to exploring the therapeutic potential of BDNF in animal models of Parkinson's disease.
    • Comments:
      Comment in: J Neurochem. 1993 Apr;60(4):1582-3. (PMID: 8455044)
    • Accession Number:
      0 (Brain-Derived Neurotrophic Factor)
      0 (Nerve Growth Factors)
      0 (Nerve Tissue Proteins)
      8HW4YBZ748 (Oxidopamine)
      9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
      GAN16C9B8O (Glutathione)
      ULW86O013H (Glutathione Disulfide)
      VTD58H1Z2X (Dopamine)
    • Publication Date:
      Date Created: 19920701 Date Completed: 19920724 Latest Revision: 20190630
    • Publication Date:
      20231215
    • Accession Number:
      10.1111/j.1471-4159.1992.tb08880.x
    • Accession Number:
      1613515