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The Journal of Neuroscience, March 15, 1999, 19(6):2008-2015
Glial Cell Line-Derived Neurotrophic Factor Rescues
Target-Deprived Sympathetic Spinal Cord Neurons But Requires
Transforming Growth Factor- as Cofactor In Vivo
Andreas
Schober1,
Richard
Hertel1,
Urmas
Arumäe2,
Lilla
Farkas1,
Jozsef
Jaszai1,
Kerstin
Krieglstein1,
Mart
Saarma2, and
Klaus
Unsicker1
1 Department of Neuroanatomy, The University of
Heidelberg, D-69120 Heidelberg, Germany, and 2 Institute of
Biotechnology, Viikki Biocenter 1, University of Helsinki, FIN-00014
Helsinki, Finland
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  receptor 1 and c-Ret receptors, which are essential for GDNF
signaling. IML neurons also display immunoreactivity for transforming
growth factor- (TGF-) 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. 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- isoforms but not GDNF. This suggests that the
presence of endogenous TGF- 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- for
permitting trophic actions of GDNF in vitro (Krieglstein
et al., 1998) also applies to the in vivo situation.
Key words:
preganglionic sympathetic neurons; intermediolateral
column; adrenal chromaffin cells; GDNF receptors; TGF- receptors; spinal cord
Copyright © 1999 Society for Neuroscience 0270-6474/99/1962008-08$05.00/0
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