dc.contributor.author | Iravani, Mahmoud M. | |
dc.contributor.author | Costa, S. | |
dc.contributor.author | Jackson, M. J. | |
dc.contributor.author | Tel, Banu C. | |
dc.contributor.author | Cannizzaro, C. | |
dc.contributor.author | Pearce, R. K. B. | |
dc.contributor.author | Jenner, P. | |
dc.date.accessioned | 2013-06-18T11:00:42Z | |
dc.date.available | 2013-06-18T11:00:42Z | |
dc.date.issued | 2001-02 | |
dc.identifier.citation | Iravani , M M , Costa , S , Jackson , M J , Tel , B C , Cannizzaro , C , Pearce , R K B & Jenner , P 2001 , ' GDNF reverses priming for dyskinesia in MPTP-treated, L-DOPA-primed common marmosets ' , European Journal of Neuroscience , vol. 13 , no. 3 , pp. 597-608 . | |
dc.identifier.issn | 0953-816X | |
dc.identifier.other | ORCID: /0000-0002-4905-9682/work/32997601 | |
dc.identifier.uri | http://hdl.handle.net/2299/10823 | |
dc.description.abstract | Parkinson's disease (PD) is associated with a progressive loss of dopamine neurons in the substantia nigra and degeneration of dopaminergic terminals in the striatum. Although L-DOPA treatment provides the most effective symptomatic relief for PD it does not prevent the progression of the disease, and its long-term use is associated with the onset of dyskinesia. In rodent and primate studies, glial cell line-derived neurotrophic factor (GDNF) may prevent 6-OHDA- or MPTP-induced nigral degeneration and so may be beneficial in the treatment of PD. In this study, we investigate the effects of GDNF on the expression of dyskinesia in L-DOPA-primed MPTP-treated common marmosets, exhibiting dyskinesia. GDNF or saline was administered by two intraventricular injections, 4 weeks apart, to MPTP-treated, L-DOPA-treated common marmosets primed to exhibit dyskinesia. Prior to GDNF or saline administration, all animals displayed marked dyskinesia when treated with L-DOPA. GDNF administration produced a significant improvement in motor disability and, following the second injection of GDNF, a significant improvement in the locomotor activity was observed. Following the administration of L-DOPA there was a greater reversal of disability and a reduction in the intensity of L-DOPA-induced dyskinesia in GDNF-treated animals compared to saline-treated controls. However, there was no significant difference in L-DOPA's ability to increase locomotor activity between GDNF-treated and saline-treated animals. GDNF treatment caused a significant increase in the number of tyrosine hydroxylase-positive neurons in the substantia nigra, but no change in [H-3]mazindol binding to dopamine terminals was found in the striatum of GDNF-treated animals compared to saline-treated controls. In GDNF-treated animals a small but significant reduction in enkephalin mRNA was observed in the caudate nucleus but not in the putamen or the nucleus accumbens. Substance P mRNA expression was equally reduced in the caudate nucleus and the putamen of the GDNF-treated animals but not in the nucleus accumbens. Intraventricular administration of GDNF improved MPTP-induced disability and reversed dopamine cell loss in the substantia nigra. GDNF also diminished L-DOPA-induced dyskinesia, which may relate to its ability to partly restore nigral dopaminergic transmission or to modify the activity of striatal output pathways. | en |
dc.format.extent | 12 | |
dc.language.iso | eng | |
dc.relation.ispartof | European Journal of Neuroscience | |
dc.subject | dyskinesia | |
dc.subject | glial cell line-derived neurotrophic factor | |
dc.subject | L-DOPA | |
dc.subject | marmoset | |
dc.subject | MPTP | |
dc.subject | Parkinson's disease | |
dc.subject | LEVODOPA-INDUCED DYSKINESIAS | |
dc.subject | NIGRAL DOPAMINERGIC-NEURONS | |
dc.subject | BOLUS INTRAVENTRICULAR-INJECTION | |
dc.subject | 6-HYDROXYDOPAMINE IN-VIVO | |
dc.subject | NEUROTROPHIC FACTOR GDNF | |
dc.subject | CELL-LINE | |
dc.subject | PARKINSONS-DISEASE | |
dc.subject | GENE-EXPRESSION | |
dc.subject | SUBSTANTIA-NIGRA | |
dc.subject | GROWTH-FACTOR | |
dc.title | GDNF reverses priming for dyskinesia in MPTP-treated, L-DOPA-primed common marmosets | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.description.status | Peer reviewed | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |