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

På svenska

Author

  • B A Horger
  • M C Nishimura
  • M P Armanini
  • L C Wang
  • K T Poulsen
  • Carl Rosenblad
  • Deniz Kirik
  • B Moffat
  • L Simmons
  • E Jr Johnson
  • J Milbrandt
  • A Rosenthal
  • Anders Björklund
  • R A Vandlen
  • M A Hynes
  • H S Phillips
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Summary, in English

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.

Publishing year

1998

Language

English

Pages

4929-4937

Publication/Series

Journal of Neuroscience

Volume

18

Issue

13

Document type

Journal article

Publisher

Society for Neuroscience

Topic

  • Neurosciences

Keywords

  • GDNF
  • dopaminergic
  • trophic
  • Parkinson's
  • nigrostriatal
  • 6-OHDA

Status

Published

Research group

  • Brain Repair and Imaging in Neural Systems (BRAINS)
  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 1529-2401