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Protection of dopaminergic nigrostriatal afferents by GDNF delivered by microspheres in a rodent model of Parkinson's disease
Synapse (New York, N.Y.), 2002-06, Vol.44 (3), p.124-131
Gouhier, Christelle
Chalon, Sylvie
Aubert-Pouessel, Anne
Venier-Julienne, Marie-Claire
Jollivet, Christophe
Benoit, Jean-Pierre
Guilloteau, Denis
2002
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Gouhier, Christelle
Chalon, Sylvie
Aubert-Pouessel, Anne
Venier-Julienne, Marie-Claire
Jollivet, Christophe
Benoit, Jean-Pierre
Guilloteau, Denis
Titel
Protection of dopaminergic nigrostriatal afferents by GDNF delivered by microspheres in a rodent model of Parkinson's disease
Ist Teil von
Synapse (New York, N.Y.), 2002-06, Vol.44 (3), p.124-131
Ort / Verlag
New York: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2002
Quelle
Wiley-Blackwell Full Collection
Beschreibungen/Notizen
The use of glial cell line‐derived neurotrophic factor (GDNF) appears to be a promising strategy to promote survival and function of the nigrostriatal dopaminergic pathway damaged in Parkinson's disease (PD). However, effective intracerebral administration is required for optimal therapeutic benefit and tools to evaluate such therapies must be developed. A rodent model of PD was therefore developed using striatal injection of 6‐hydroxydopamine (6‐OHDA) with simultaneous implantation of GDNF‐delivering microspheres. The effects of GDNF released from microspheres were assessed by classical methods such as amphetamine‐induced rotating behavior and tyrosine hydroxylase (TH) immunoreactivity, as well as by quantitative autoradiography using PE2I, a dopamine transporter (DAT) radiotracer, which is also suitable for SPET imaging in humans. 6‐OHDA‐lesioned animals that received microspheres without GDNF were used as controls. During the first 3 weeks after simultaneous lesion and implantation, the amphetamine‐induced rotating behavior of GDNF‐treated rats was improved compared to controls and an increase in TH expression (+26%) was measured in the striatum 6 weeks after lesion. In accordance with these results, an increase in striatal PE2I‐labeled DAT density was obtained (+17%) after 3 and 6 weeks of treatment. In conclusion, this study demonstrates the neuroprotective action of GDNF delivered by microspheres and suggests that PE2I may be an appropriate radiotracer for use in SPET scintigraphy to follow up treatment of PD in humans. Synapse 44:124–131, 2002. © 2002 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0887-4476
eISSN: 1098-2396
DOI: 10.1002/syn.10063
Titel-ID: cdi_proquest_miscellaneous_71596120
Format
–
Schlagworte
6-hydroxydopamine
,
amphetamine
,
Animals
,
Corpus Striatum - drug effects
,
Corpus Striatum - metabolism
,
Disease Models, Animal
,
Dopamine - metabolism
,
Dopamine Plasma Membrane Transport Proteins
,
dopamine transporter
,
Glial Cell Line-Derived Neurotrophic Factor
,
Male
,
Membrane Glycoproteins
,
Membrane Transport Proteins - metabolism
,
Microspheres
,
Nerve Growth Factors
,
Nerve Tissue Proteins - administration & dosage
,
Neurons, Afferent - drug effects
,
Neurons, Afferent - metabolism
,
Neuroprotective Agents - administration & dosage
,
Parkinson Disease - drug therapy
,
Parkinson Disease - metabolism
,
PE2I
,
Rats
,
Rats, Wistar
,
Substantia Nigra - drug effects
,
Substantia Nigra - metabolism
,
tyrosine hydroxylase
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