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Brain‐derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from 2,4,5‐trihydroxyphenylalanine‐induced injury
Author(s) -
Skaper Stephen D.,
Negro A.,
Facci L.,
Toso R. Dal
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490340413
Subject(s) - dopaminergic , tyrosine hydroxylase , neurotrophic factors , dopamine , brain derived neurotrophic factor , population , neuroscience , basal forebrain , neurotoxicity , endocrinology , biology , chemistry , medicine , central nervous system , toxicity , receptor , environmental health
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.