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Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 19(6)
- Publication Year :
- 1999
-
Abstract
- 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 situhybridization revealed that IML neurons express the glycosylphosphatidylinositol-linked α receptor 1 and c-Ret receptors, which are essential for GDNF signaling. IML neurons also display immunoreactivity for transforming growth factor-β (TGF-β) receptor II. Administration of GDNF (recombinant human, 1 μg) in Gelfoam implanted into the medullectomized adrenal gland rescued all Fluoro-Gold-labeled preganglionic neurons projecting to the adrenal medulla after four weeks. Cytochromecapplied 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-β isoforms but not GDNF. This suggests that the presence of endogenous TGF-β 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-β for permitting trophic actions of GDNFin vitro(Krieglstein et al., 1998) also applies to thein vivosituation.
- Subjects :
- Male
medicine.medical_specialty
Sympathetic nervous system
Glial Cell Line-Derived Neurotrophic Factor Receptors
Sympathetic Nervous System
Autonomic Fibers, Preganglionic
Nerve Tissue Proteins
Article
03 medical and health sciences
0302 clinical medicine
Neurotrophic factors
Transforming Growth Factor beta
Internal medicine
Proto-Oncogene Proteins
Adrenal Glands
Glial cell line-derived neurotrophic factor
medicine
Animals
Drosophila Proteins
Humans
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors
Rats, Wistar
030304 developmental biology
Neurons
0303 health sciences
biology
urogenital system
General Neuroscience
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Biological Transport
Rats
medicine.anatomical_structure
Endocrinology
Nerve growth factor
nervous system
Spinal Cord
Adrenal Medulla
biology.protein
Adrenal medulla
GDNF family of ligands
030217 neurology & neurosurgery
Neurotrophin
Subjects
Details
- ISSN :
- 02706474
- Volume :
- 19
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....c1c2fd853c70fbcaba791c569675125a