Brain‐derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from 2,4,5‐trihydroxyphenylalanine‐induced injury

Brain‐derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from... Brain‐derived neurotrophic factor (BDNF) supports the survival of sensory neurons as well as retinal ganglion cells, basal forebrain cholinergic neurons, and mesencephalic dopaminergic neurons in vitro. Here we examined the ability of BDNF to confer protection on cultured dopaminergic neurons against the neurotoxic effects of 6‐hydroxyDOPA (TOPA or 2,3,5,‐trihydroxyphenylalanine), a metabolite of the dopamine pathway suggested to participate in the pathology of Parkinson's disease. Cells prepared from embryonic day 14–15 rat mesencephalon were maintained with 10–50 ng/ml BDNF for 7 days prior to addition of TOPA (10–30 μM) for 24 hr. In BDNF‐treated cultures, the extensive loss ( >90%) of tyrosine hydroxylase immunopositive cells was virtually (<10%) eliminated, while the equally drastic loss (>90%) of the overall cell population was limited to only a 25–30% recovery. Furthermore, the monosialoganglioside GM1 (1–10 μM), although inactive alone, acted synergistically with subthreshold amounts of BDNF to rescue tyrosine hydroxylase‐positive cells against TOPA neurotoxicity. These results add impetus to exploring the therapeutic potential of gangliosides and BDNF in Parkinson's disease. © 1993 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

Brain‐derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from 2,4,5‐trihydroxyphenylalanine‐induced injury

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Publisher
Wiley
Copyright
Copyright © 1993 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/jnr.490340413
Publisher site
See Article on Publisher Site

Abstract

Brain‐derived neurotrophic factor (BDNF) supports the survival of sensory neurons as well as retinal ganglion cells, basal forebrain cholinergic neurons, and mesencephalic dopaminergic neurons in vitro. Here we examined the ability of BDNF to confer protection on cultured dopaminergic neurons against the neurotoxic effects of 6‐hydroxyDOPA (TOPA or 2,3,5,‐trihydroxyphenylalanine), a metabolite of the dopamine pathway suggested to participate in the pathology of Parkinson's disease. Cells prepared from embryonic day 14–15 rat mesencephalon were maintained with 10–50 ng/ml BDNF for 7 days prior to addition of TOPA (10–30 μM) for 24 hr. In BDNF‐treated cultures, the extensive loss ( >90%) of tyrosine hydroxylase immunopositive cells was virtually (<10%) eliminated, while the equally drastic loss (>90%) of the overall cell population was limited to only a 25–30% recovery. Furthermore, the monosialoganglioside GM1 (1–10 μM), although inactive alone, acted synergistically with subthreshold amounts of BDNF to rescue tyrosine hydroxylase‐positive cells against TOPA neurotoxicity. These results add impetus to exploring the therapeutic potential of gangliosides and BDNF in Parkinson's disease. © 1993 Wiley‐Liss, Inc.

Journal

Journal of Neuroscience ResearchWiley

Published: Mar 1, 1993

References

  • Gangliosides in the nervous system
    Ando, Ando
  • Structure‐activity relations of excitatory amino acids on frog and rat spinal neurons
    Biscoe, Biscoe; Evans, Evans; Headley, Headley; Martin, Martin; Watkins, Watkins
  • Function and evolution in the NGF family and its receptors
    Ebendal, Ebendal
  • Role of glycine in the N‐methyl‐D‐aspartate‐mediated neuronal cytotoxicity
    Patel, Patel; Zinkand, Zinkand; Thompson, Thompson; Keith, Keith; Salama, Salama

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