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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for several populations of CNS and peripheral neurons. Synthesis and storage of GDNF by the neuron-like adrenal medullary cells suggest roles in adrenal functions and/or in the maintenance of spinal cord neurons that innervate the adrenal medulla. We show that unilateral adrenomedullectomy causes degeneration of all sympathetic preganglionic neurons within the intermediolateral column (IML) of spinal cord segments T7-T10 that project to the adrenal medulla. In situ hybridization revealed that IML neurons express the glycosylphosphatidylinositol-linked alpha receptor 1 and c-Ret receptors, which are essential for GDNF signaling. IML neurons also display immunoreactivity for transforming growth factor-beta (TGF-beta) receptor II. Administration of GDNF (recombinant human, 1 microg) in Gelfoam implanted into the medullectomized adrenal gland rescued all Fluoro-Gold-labeled preganglionic neurons projecting to the adrenal medulla after four weeks. Cytochrome c applied as a control protein was not effective. The protective effect of GDNF was prevented by co-administration to the Gelfoam of neutralizing antibodies recognizing all three TGF-beta isoforms but not GDNF. This suggests that the presence of endogenous TGF-beta was essential for permitting a neurotrophic effect of GDNF. Our data indicate that GDNF has a capacity to protect a population of autonomic spinal cord neurons from target-deprived cell death. Furthermore, our results demonstrate for the first time that the previously reported requirement of TGF-beta for permitting trophic actions of GDNF in vitro (Kreiglstein et al., 1998) also applies to the in vivo situation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GDNF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ret oncogene protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Ret protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0270-6474
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2008-15
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10066254-Adrenal Glands,
pubmed-meshheading:10066254-Adrenal Medulla,
pubmed-meshheading:10066254-Animals,
pubmed-meshheading:10066254-Autonomic Fibers, Preganglionic,
pubmed-meshheading:10066254-Biological Transport,
pubmed-meshheading:10066254-Drosophila Proteins,
pubmed-meshheading:10066254-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:10066254-Glial Cell Line-Derived Neurotrophic Factor Receptors,
pubmed-meshheading:10066254-Humans,
pubmed-meshheading:10066254-Male,
pubmed-meshheading:10066254-Nerve Growth Factors,
pubmed-meshheading:10066254-Nerve Tissue Proteins,
pubmed-meshheading:10066254-Neurons,
pubmed-meshheading:10066254-Proto-Oncogene Proteins,
pubmed-meshheading:10066254-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:10066254-Rats,
pubmed-meshheading:10066254-Rats, Wistar,
pubmed-meshheading:10066254-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:10066254-Spinal Cord,
pubmed-meshheading:10066254-Sympathetic Nervous System,
pubmed-meshheading:10066254-Transforming Growth Factor beta
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pubmed:year |
1999
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pubmed:articleTitle |
Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo.
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pubmed:affiliation |
Department of Neuroanatomy, The University of Heidelberg, D-69120 Heidelberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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