Long-term effect of intra-striatal glial cell line-derived neurotrophic factor-releasing microspheres in a partial rat model of Parkinson's disease.
Glial cell line-derived neurotrophic factor (GDNF) offers the possibility to stimulate axonal regeneration of mesencephalic dopaminergic neurons, which are affected in Parkinson's disease. Nevertheless, a safe and efficient GDNF delivery system that may be used in clinical trials is still lacking. In a previous study, we showed that GDNF-releasing microspheres can deliver the neurotrophic factor for 2 months, allowing in a partial rat model of Parkinson's disease a sprouting of the preserved dopaminergic fibers and functional improvement 8 weeks after the treatment. The present study confirms these previous observations and shows that the amphetamine-induced rotation score is still decreased 24 weeks after the end of GDNF delivery. Nevertheless, the improvement was not statistically significant at the latest time point due to the spontaneous reinnervation observed in the model used.
Jollivet
Christophe
C
INSERM ERIT-M 0104, Bâtiment IBT, 10 rue Andre Boquel, 49100 Angers, France.
Aubert-Pouessel
Anne
A
Clavreul
Anne
A
Venier-Julienne
Marie-Claire
MC
Montero-Menei
Claudia N
CN
Benoit
Jean-Pierre
JP
Menei
Philippe
P
D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry / Q000379:methods; D008863:Microspheres; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects; D013995:Time; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase