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Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells

Authors

  • Pedro Barroso-Chinea,

    1. Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, 38207 La Laguna,Tenerife, Spain
    2. Unidad de Investigación del Hospital Universitario de Canarias, Tenerife, Spain
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  • Ignacio Cruz-Muros,

    1. Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, 38207 La Laguna,Tenerife, Spain
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  • María S. Aymerich,

    1. Departamento de Bioquímica, Clínica Universitaria y Facultad de Medicina, Universidad de Navarra, Centro de Investigación Medica Aplicada, Pamplona, Spain
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  • Manuel Rodríguez-Díaz,

    1. Departamento de Fisiología, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain
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  • Domingo Afonso-Oramas,

    1. Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, 38207 La Laguna,Tenerife, Spain
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  • José L. Lanciego,

    1. Departamento de Anatomía, Clínica Universitaria y Facultad de Medicina, Universidad de Navarra, Centro de Investigación Medica Aplicada, Pamplona, Spain
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  • Tomás González-Hernández

    1. Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, 38207 La Laguna,Tenerife, Spain
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Dr Tomás González Hernández, as above.
E-mail: tgonhern@ull.es

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-β superfamily that when exogenously administrated exerts a potent trophic action on dopaminergic (DA) cells. Although we know a lot about its signalling mechanisms and pharmacological effects, physiological actions of GDNF on the adult brain remain unclear. Here, we have used morphological and molecular techniques, and an experimental model of Parkinson's disease in rats, to investigate whether GDNF constitutively expressed in the adult mesostriatal system plays a neuroprotective role on midbrain DA cells. We found that although all midbrain DA cells express both receptor components of GDNF (GFRα1 and Ret), those in the ventral tegmental area (VTA) and rostromedial substantia nigra (SNrm) also contain GDNF but not GDNFmRNA. The levels of GDNFmRNA are significantly higher in the ventral striatum (vSt), the target region of VTA and SNrm cells, than in the dorsal striatum (dSt), the target region of DA cells in the caudoventral substantia nigra (SNcv). After fluoro-gold injection in striatum, VTA and SNrm DA cells show triple labelling for tyrosine hydroxylase, GDNF and fluoro-gold, and after colchicine injection in the lateral ventricle, they become GDNF-immunonegative, suggesting that GDNF in DA somata comes from their striatal target. As DA cells in VTA and SNrm are more resistant than those in SNcv to intracerebroventricular injection of 6-OHDA, as occurs in Parkinson's disease, we can suggest that the fact that they project to vSt, where GDNF expression is significantly higher than in the dSt, is a neuroprotective factor involved in the differential vulnerability of midbrain DA neurons.

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