GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain following intracerebroventricular or intraparenchymal administration.
BACKGROUND
Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a survival and neuroprotective factor for nigrostriatal dopaminergic neurons in vivo. The present study was designed to investigate the possible neuroprotective and restorative role by GDNF for dopaminergic neurons which were exposed to the neurotoxin 6-hydroxydopamine (6-OHDA).


METHODS
We compared neurochemical, morphological and behavioural changes following striatal infusion of GDNF to those following intracerebroventricular (i.c.v.) infusion.


RESULTS
Apomorphine-induced rotation showed significant recovery after both types of infusion. Significant recovery of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons and fibers were found in the substantia nigra and striatum following both striatum and i.c.v. infusion except for the number of TH-IR neurons in the i.c.v. infusion group.


CONCLUSIONS
These results suggest that GDNF induces recovery of the nigrostriatal dopaminergic system, and this indicates a potential usefulness of GDNF for the treatment of Parkinson's disease.
Aoi
M
M
Department of Neurological Surgery, Okayama University Medical School, Japan.
Date
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Tomita
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Ohmoto
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D018663:Adrenergic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D007276:Injections, Intraventricular; D009457:Neuroglia / Q000737:chemistry* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D016627:Oxidopamine / Q000008:administration & dosage / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D014793:Visual Cortex / Q000166:cytology / Q000187:drug effects / Q000473:pathology*
D018663:Adrenergic Agents; D019208:Brain-Derived Neurotrophic Factor; D011954:Receptors, Dopamine; D016627:Oxidopamine