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Titolo:
Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo
Autore:
Schober, A; Hertel, R; Arumae, U; Farkas, L; Jaszai, J; Krieglstein, K; Saarma, M; Unsicker, K;
Indirizzi:
Univ Heidelberg, Dept Neuroanat, D-69120 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69120 , D-69120 Heidelberg, Germany UnivdHelsinki, Inst Biotechnol, Viikki Bioctr 1, FIN-00014 Helsinki, Finlan Univ Helsinki Helsinki Finland FIN-00014 r 1, FIN-00014 Helsinki, Finlan
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 6, volume: 19, anno: 1999,
pagine: 2008 - 2015
SICI:
0270-6474(19990315)19:6<2008:GCLNFR>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RETROGRADE AXONAL-TRANSPORT; MICE LACKING GDNF; PREGANGLIONIC NEURONS; ADRENAL-GLAND; MESSENGER-RNA; TGF-BETA; CHROMAFFIN CELLS; SENSORY NEURONS; NERVOUS-TISSUE; TROPHIC ROLE;
Keywords:
preganglionic sympathetic neurons; intermediolateral column; adrenal chromaffin cells; GDNF receptors; TGF-beta receptors; spinal cord;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Unsicker, K UnivGermanyberg, Dept Neuroanat, Neuenheimer Feld 307, D-69120Heidelberg, Univ Heidelberg Neuenheimer Feld 307 Heidelberg Germany D-69120
Citazione:
A. Schober et al., "Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo", J NEUROSC, 19(6), 1999, pp. 2008-2015

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 rolesin adrenal functions and/or in the maintenance of spinal cord neurons thatinnervate 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 mu g) 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 (Krieglstein et al., 1998) also applies to the in vivo situation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 14:57:33