Advanced

Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons

Horger, B A; Nishimura, M C; Armanini, M P; Wang, L C; Poulsen, K T; Rosenblad, Carl; Kirik, Deniz LU ; Moffat, B; Simmons, L and Johnson, E Jr, et al. (1998) In Journal of Neuroscience 18(13). p.4929-4937
Abstract
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on... (More)
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GDNF, dopaminergic, trophic, Parkinson's, nigrostriatal, 6-OHDA
in
Journal of Neuroscience
volume
18
issue
13
pages
4929 - 4937
publisher
Society for Neuroscience
external identifiers
  • pmid:9634558
  • scopus:0032125462
ISSN
1529-2401
language
English
LU publication?
yes
id
17ddbafe-dbc1-4af7-b383-9d7d4cc22b93 (old id 1113838)
alternative location
http://www.jneurosci.org/cgi/content/full/18/13/4929
date added to LUP
2008-07-16 12:21:07
date last changed
2017-10-01 04:52:23
@article{17ddbafe-dbc1-4af7-b383-9d7d4cc22b93,
  abstract     = {Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.},
  author       = {Horger, B A and Nishimura, M C and Armanini, M P and Wang, L C and Poulsen, K T and Rosenblad, Carl and Kirik, Deniz and Moffat, B and Simmons, L and Johnson, E Jr and Milbrandt, J and Rosenthal, A and Björklund, Anders and Vandlen, R A and Hynes, M A and Phillips, H S},
  issn         = {1529-2401},
  keyword      = {GDNF,dopaminergic,trophic,Parkinson's,nigrostriatal,6-OHDA},
  language     = {eng},
  number       = {13},
  pages        = {4929--4937},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons},
  volume       = {18},
  year         = {1998},
}