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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-2-21
pubmed:abstractText
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Both glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) play key roles in maintaining the DAergic phenotype and exert a cytoprotective effect on these neurons in vivo and in vitro. However, controversy still exists regarding the relative potency of the two factors and the extent to which they act synergistically. In this study, we used a refined version of organotypic cultures as a model for PD. The neurotoxin 6-hydroxydopamine (6-OHDA) was applied unilaterally in slices of rat mesencephalon, allowing for internal controls and enabling a precise comparison between the two sides of the midbrain. We evaluated the cytoprotective and regenerative effects of BDNF, GDNF and the combination of these in terms of surviving tyrosine hydroxylase positive (TH+) cells and TH mRNA expression. Pre-, co-, or post-treatment with neurotrophic factors clearly protects DAergic neurons from cell death. Cell survival is particularly pronounced in cultures pre-treated with BDNF and is not further increased when BDNF is applied in combination with GDNF in equimolar dose. On the lesion side, surviving TH+ cells exposed to neurotrophic factors showed extensive sprouting, and BDNF treatment resulted in a two-fold increase in TH mRNA. Such effects were not seen in the absence of toxin exposure. Thus, we observed that BDNF induced an upregulation of the DAergic phenotype, which suggest a cytoprotective and regenerative effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
1378
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-18
pubmed:meshHeading
pubmed-meshheading:21236244-Adrenergic Agents, pubmed-meshheading:21236244-Animals, pubmed-meshheading:21236244-Brain-Derived Neurotrophic Factor, pubmed-meshheading:21236244-Dopamine, pubmed-meshheading:21236244-Female, pubmed-meshheading:21236244-Fluorescent Antibody Technique, pubmed-meshheading:21236244-Glial Cell Line-Derived Neurotrophic Factor, pubmed-meshheading:21236244-Immunohistochemistry, pubmed-meshheading:21236244-Male, pubmed-meshheading:21236244-Mesencephalon, pubmed-meshheading:21236244-Microscopy, Confocal, pubmed-meshheading:21236244-Neurons, pubmed-meshheading:21236244-Neuroprotective Agents, pubmed-meshheading:21236244-Organ Culture Techniques, pubmed-meshheading:21236244-Oxidopamine, pubmed-meshheading:21236244-Parkinson Disease, pubmed-meshheading:21236244-Rats, pubmed-meshheading:21236244-Rats, Wistar, pubmed-meshheading:21236244-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2011
pubmed:articleTitle
Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease.
pubmed:affiliation
Centre of Molecular Biology and Neuroscience (CMBN), University of Oslo, P.O. Box 1105 Blindern, NO-0317 Oslo, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't