ParkinsonFranceV1, Main, Exploration, bibRecordById, Pascal:95-0514048

Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum

Identifieur interne : 004891 ( Main/Exploration ); précédent : 004890; suivant : 004892

Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum

Auteurs : M.-T. Herrero [Espagne] ; S. J. Augood ; E. C. Hirsch [France] ; F. Javoy-Agid [France] ; M. R. Luquin [Espagne] ; Yves Agid [France] ; J. A. Obeso [Espagne] ; P. C. Emson

Source :

Neuroscience [ 0306-4522 ] ; 1995.

RBID : Pascal:95-0514048

Descripteurs français

Pascal (Inist)
- Dopa, Préproenképhaline, Tachykinine, Neurotoxine, Corps strié, Expression génique, Antiparkinsonien, Traitement, Parkinson maladie, Animal, Pathologie expérimentale, Singe, MPTP.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- Animal, Antiparkinson agent, Corpus striatum, Dopa, Experimental disease, Gene expression, Monkey, Neurotoxin, Parkinson disease, Preproenkephalin, Tachykinin, Treatment.

Abstract

The cellular expression of the genes encoding the neuropeptides enkephalin and substance P were examined in the caudate nucleus and putamen of parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by in situ hybridization using radioactive antisense oligonucleotides coupled with computer-assisted image analysis. Behavioural evaluation of the animals revealed two levels of motor impairment ; one group moderately impaired and the other severely disabled. A marked increase in the cellular content of preproenkephalin A messenger RNA was observed in medium-sized (106±9 μm²) cells in the caudate-putamen of all MPTP animals when compared with controls, the increase being greatest in the most severely impaired animals. By contrast, a marked reduction in the cellular abundance of preprotachykinin gene expression was detected in striatal cells (101±16 μm²) of these same MPTP animals. These changes in neuropeptide gene expression were not associated with a change in the density (approximately 10 cells per mm²) of messenger RNA-expressing cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in a dissociation of expression of these two genes : the cellular abundance of preproenkephalin A remained elevated whilst preprotachykinin levels were normalized and comparable with controls. No change in the cellular abundance of preprotachykinin messenger RNA was observed in cells of the insular cortex or a small discrete population of large cells (208 ± 27 μm²) in the ventral putamen. These results demonstrate that MPTP treatment of primates results in a marked potentiation in preproenkephalin messenger RNA coupled with an attenuation in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L-DOPA therapy given on an intermittent schedule reverses the decrease in preprotachykinin messenger RNA, but fails to reverse the increase in preproenkephalin messenger RNA in the same animal. These observations suggest that a dissociation of the activity of these two neuropeptide systems may underlie the improvement in motor skill that accompanies dopamine replacement therapy and that this dissociation may well be instrumental in the long-term complications associated with L-DOPA therapy.

Affiliations:

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Le document en format XML

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<front><div type="abstract" xml:lang="en">The cellular expression of the genes encoding the neuropeptides enkephalin and substance P were examined in the caudate nucleus and putamen of parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by in situ hybridization using radioactive antisense oligonucleotides coupled with computer-assisted image analysis. Behavioural evaluation of the animals revealed two levels of motor impairment ; one group moderately impaired and the other severely disabled. A marked increase in the cellular content of preproenkephalin A messenger RNA was observed in medium-sized (106±9 μm<sup>2</sup>
) cells in the caudate-putamen of all MPTP animals when compared with controls, the increase being greatest in the most severely impaired animals. By contrast, a marked reduction in the cellular abundance of preprotachykinin gene expression was detected in striatal cells (101±16 μm<sup>2</sup>
) of these same MPTP animals. These changes in neuropeptide gene expression were not associated with a change in the density (approximately 10 cells per mm<sup>2</sup>
) of messenger RNA-expressing cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in a dissociation of expression of these two genes : the cellular abundance of preproenkephalin A remained elevated whilst preprotachykinin levels were normalized and comparable with controls. No change in the cellular abundance of preprotachykinin messenger RNA was observed in cells of the insular cortex or a small discrete population of large cells (208 ± 27 μm<sup>2</sup>
) in the ventral putamen. These results demonstrate that MPTP treatment of primates results in a marked potentiation in preproenkephalin messenger RNA coupled with an attenuation in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L-DOPA therapy given on an intermittent schedule reverses the decrease in preprotachykinin messenger RNA, but fails to reverse the increase in preproenkephalin messenger RNA in the same animal. These observations suggest that a dissociation of the activity of these two neuropeptide systems may underlie the improvement in motor skill that accompanies dopamine replacement therapy and that this dissociation may well be instrumental in the long-term complications associated with L-DOPA therapy.</div>
</front>
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Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum

Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri