Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy)
Identifieur interne : 003A62 ( Main/Exploration ); précédent : 003A61; suivant : 003A63Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy)
Auteurs : C. Scherfler [Autriche] ; Z. Puschban [Autriche] ; I. Ghorayeb [France] ; G. P Goebel [Autriche] ; F. Tison [France] ; K. Jellinger [Autriche] ; Werner Poewe [Autriche] ; G. K Wenning [Autriche]Source :
- Neuroscience [ 0306-4522 ] ; 2000.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- 6-OHDA, 6-hydroxydopamine, 6-hydroxydopamine, AChE, acetylcholinesterase, Animal model, DAB, diaminobenzidine tetrahydrochloride, Degeneration, GCI, glial cytoplasmic inclusion, GFAP, glial fibrillary acidic protein, HD, Huntington’s disease, HE, hematoxylin–eosin, Lesion, MFB, medial forebrain bundle, MSA, multiple system atrophy, MSA-P, MSA-Parkinson subtype, Multiple system atrophy, Nigrostriatal pathway, PBS, phosphate-buffered saline, PD, Parkinson’s disease, Parkinson disease, QA, quinolinic acid, Rat, SND, striatonigral degeneration, SNc, substantia nigra pars compacta, TH, tyrosine hydroxylase, balance test, neuroprotection, quinolinic acid, staircase test, stepping test.
Abstract
This study characterizes paw reaching, stepping and balance abnormalities in a double lesion rat model of striatonigral degeneration, the core pathology underlying levodopa unresponsive parkinsonism associated with multiple system atrophy. Extensive unilateral nigral or striatal lesions induced by 6-hydroxydopamine or quinolinic acid, respectively, produced a similarly marked contralateral paw reaching deficit without further deterioration following a secondary (complementary) lesion of ipsilateral striatum or substantia nigra. Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions without further deterioration following the secondary striatal lesion. In contrast, initial unilateral striatal quinolinic acid injections induced bilateral stepping deficits that significantly worsened contralaterally following the secondary nigral lesion. Contralateral sidefalling rates were significantly increased following primary nigral and striatal lesions. Secondary nigral but not secondary striatal lesions worsened contralateral sidefalling rates. Histological studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia nigra pars compacta and variable degrees of striatal degeneration depending on the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed significantly larger residual striatal surface areas following the secondary striatal quinolinic acid lesion compared to animals with primary striatal quinolinic acid lesions (P<0.001). These findings are in line with previous experimental studies demonstrating that striatal dopamine depletion confers neuroprotection against subsequent excitotoxic injury. Whether loss of dopaminergic neurons protects against the striatal disease process occurring in multiple system atrophy (Parkinson-type) remains to be elucidated. In summary, this is the first experimental study to investigate spontaneous motor behaviour in a unilateral double lesion rat model. Our observations are consistent with a complex interaction of nigral and striatal lesions producing distinct behavioural and histological changes depending on the lesion sequence. Tests of forelimb akinesia and complex motor behaviour appear to provide a reliable tool that will be helpful for monitoring the effects of interventional strategies such as embryonic neuronal transplantation in the rat model of striatonigral degeneration.
Url:
DOI: 10.1016/S0306-4522(00)00171-8
Affiliations:
- Autriche, France
- Aquitaine, Nouvelle-Aquitaine, Tyrol (Land), Vienne (Autriche)
- Bordeaux, Innsbruck, Vienne (Autriche)
- Université de médecine d'Innsbruck
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Le document en format XML
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<front><div type="abstract" xml:lang="en">This study characterizes paw reaching, stepping and balance abnormalities in a double lesion rat model of striatonigral degeneration, the core pathology underlying levodopa unresponsive parkinsonism associated with multiple system atrophy. Extensive unilateral nigral or striatal lesions induced by 6-hydroxydopamine or quinolinic acid, respectively, produced a similarly marked contralateral paw reaching deficit without further deterioration following a secondary (complementary) lesion of ipsilateral striatum or substantia nigra. Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions without further deterioration following the secondary striatal lesion. In contrast, initial unilateral striatal quinolinic acid injections induced bilateral stepping deficits that significantly worsened contralaterally following the secondary nigral lesion. Contralateral sidefalling rates were significantly increased following primary nigral and striatal lesions. Secondary nigral but not secondary striatal lesions worsened contralateral sidefalling rates. Histological studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia nigra pars compacta and variable degrees of striatal degeneration depending on the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed significantly larger residual striatal surface areas following the secondary striatal quinolinic acid lesion compared to animals with primary striatal quinolinic acid lesions (P<0.001). These findings are in line with previous experimental studies demonstrating that striatal dopamine depletion confers neuroprotection against subsequent excitotoxic injury. Whether loss of dopaminergic neurons protects against the striatal disease process occurring in multiple system atrophy (Parkinson-type) remains to be elucidated. In summary, this is the first experimental study to investigate spontaneous motor behaviour in a unilateral double lesion rat model. Our observations are consistent with a complex interaction of nigral and striatal lesions producing distinct behavioural and histological changes depending on the lesion sequence. Tests of forelimb akinesia and complex motor behaviour appear to provide a reliable tool that will be helpful for monitoring the effects of interventional strategies such as embryonic neuronal transplantation in the rat model of striatonigral degeneration.</div>
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