GDNF protects against 6-OHDA nigrostriatal lesion: in vivo study with microdialysis and PET.
We have investigated whether glial cell line-derived neurotrophic factor (GDNF) protects against a complete unilateral 6-hydroxydopamine (6-OHDA) nigrostriatal lesion, a robust rat model of Parkinson's disease. GDNF or vehicle were administered above the rat substantia nigra and into the lateral ventricle immediately before an ipsilateral 6-OHDA injection into the medial forebrain bundle. In vivo tests were employed to assess the effects of the treatment: microdialysis to measure striatal dopamine release, amphetamine challenge to estimate turning behaviour, and positron emission tomography (PET) to image dopamine reuptake sites. The present results show that GDNF can protect dopaminergic neurones against an acute and irreversible 6-OHDA lesion. They are encouraging for potential use of GDNF in Parkinson's disease.
Opacka-Juffry
J
J
MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.
Ashworth
S
S
Hume
S P
SP
Martin
D
D
Brooks
D J
DJ
Blunt
S B
SB
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*; D014055:Tomography, Emission-Computed
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D004298:Dopamine