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

In English

Författare

  • 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
Visa allt

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.

Publiceringsår

1998

Språk

Engelska

Sidor

4929-4937

Publikation/Tidskrift/Serie

Journal of Neuroscience

Volym

18

Issue

13

Dokumenttyp

Artikel i tidskrift

Förlag

Society for Neuroscience

Ämne

  • Neurosciences

Nyckelord

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

Status

Published

Forskningsgrupp

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

ISBN/ISSN/Övrigt

  • ISSN: 1529-2401