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Delayed infusion of GDNF promotes recovery of motor function in the partial lesion model of Parkinson's disease

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Author

Summary, in English

Here we studied the effects of glial cell line-derived neurotrophic factor (GDNF) in a rat model that represents the symptomatic stages of Parkinson's disease. GDNF was infused starting 2 weeks after an intrastriatal 6-hydroxydopamine (6-OHDA) lesion in order to halt the ongoing degeneration of the nigrostriatal dopaminergic neurons. GDNF or vehicle was infused in the striatum or the lateral ventricle via an osmotic minipump over a total 4-week period (2-6 weeks postlesion). Motor function was evaluated by the stepping, paw reaching and drug-induced motor asymmetry tests before the pump infusion was initiated, and was repeated once during (5 weeks postlesion) and twice after the withdrawal of the minipumps (7 and 11 weeks postlesion). We found that within two weeks following the lesion approximately 40% of the nigral TH-positive neurons were lost. In the vehicle infusion groups there was an additional 20% cell loss between 2 and 12 weeks after the lesion. This latter cell loss occurred mainly in the caudal part of the SN whereas the cell loss in the rostral SN was almost complete within the first two weeks. Ventricular GDNF infusion completely blocked the late degenerating neurons in the caudal SN and had long lasting behavioural effects on the stepping test and amphetamine rotation, extending to 6 weeks after withdrawal of the factor. Striatal infusion affected the motor behaviour transiently during the infusion period but the motor performance of these animals returned to baseline upon cessation of the GDNF delivery, and the delayed nigral cell loss was marginally affected. We conclude that intraventricular GDNF can successfully block the already initiated degenerative process in the substantia nigra, and that the effects achieved via the striatal route, when GDNF is given acutely after the lesion, diminish as the fibre terminal degeneration proceeds.

Publishing year

2001

Language

English

Pages

1589-1599

Publication/Series

European Journal of Neuroscience

Volume

13

Issue

8

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Neurosciences

Keywords

  • 6-hydroxydopamine
  • cell death
  • glial cell line-derived neurotrophic factor
  • Parkinson's disease
  • paw use
  • sensorimotor behaviour
  • stepping
  • stereology
  • tyrosine hydroxylase

Status

Published

Research group

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

ISBN/ISSN/Other

  • ISSN: 1460-9568