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Titolo:
Comparison of unilateral and bilateral intrastriatal 6-hydroxydopamine-induced axon terminal lesions: Evidence for interhemispheric functional coupling of the two nigrostriatal pathways
Autore:
Roedter, A; Winkler, C; Samii, M; Walter, GF; Brandis, A; Nikkhah, G;
Indirizzi:
Nordstadt Hosp, Neurosurg Clin, D-30167 Hannover, Germany Nordstadt Hosp Hannover Germany D-30167 Clin, D-30167 Hannover, Germany Hannover Med Sch, Neurol Clin, D-30625 Hannover, Germany Hannover Med SchHannover Germany D-30625 lin, D-30625 Hannover, Germany Hannover Med Sch, Inst Neuropathol, D-30625 Hannover, Germany Hannover MedSch Hannover Germany D-30625 hol, D-30625 Hannover, Germany
Titolo Testata:
JOURNAL OF COMPARATIVE NEUROLOGY
fascicolo: 2, volume: 432, anno: 2001,
pagine: 217 - 229
SICI:
0021-9967(20010402)432:2<217:COUABI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
SKILLED FORELIMB USE; RAT PARKINSON-MODEL; STRIATAL DOPAMINE DEPLETIONS; REACTION-TIME PERFORMANCE; SUBSTANTIA-NIGRA; BEHAVIORAL RECOVERY; NUCLEUS-ACCUMBENS; CAUDATE-NUCLEUS; STAIRCASE TEST; NEONATAL RATS;
Keywords:
Parkinson's disease; neurodegeneration; basal ganglia; dopamine; skilled forelimb use; stepping;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Nikkhah, G Nordstadt Hosp, Neurosurg Clin, Haltenhoffstr 41, D-30167 Hannover, Germany Nordstadt Hosp Haltenhoffstr 41 Hannover Germany D-30167 rmany
Citazione:
A. Roedter et al., "Comparison of unilateral and bilateral intrastriatal 6-hydroxydopamine-induced axon terminal lesions: Evidence for interhemispheric functional coupling of the two nigrostriatal pathways", J COMP NEUR, 432(2), 2001, pp. 217-229

Abstract

Partial lesions of the nigrostriatal dopamine system can be induced reliably by the intrastriatal injection of 6-hydroxydopamine (6-OHDA) and are considered to be analogous to the early stages of human Parkinson's disease. Previous studies have established a clear correlation between different doses and placements of the 6-OHDA toxin and the degree of neurodegenerative changes and behavioral impairments. In the present study, the influence of the interdependence between the two nigrostriatal systems in both hemisphereson the effects on sensorimotor behavioral performances after terminal 6-OHDA lesions was investigated. The behavioral effects were correlated to the extent of nigral dopamine neuron cell and striatal tyrosine-hydroxylase (TH)-positive fiber loss. Sprague-Dawley rats receiving unilateral intrastriatal 6-OHDA injections (4 x 5 mug) exhibited a 30-70% reduction in striatal TH-positive fiber density along an anterior-posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of behavioral impairments as revealed by amphetamine-induced rotational asymmetry, and a reduced performance in the stepping and postural balance tests. When the same amount of toxin was injected twice into both hemispheres (2 x 4 x 5 mug), additional behavioral deficits were observed, consisting of a significant, but temporary,weight loss, a stable reduction in general locomotor activity and explorational behavior, and a long-term deficit in skilled forelimb use. This is interesting in light of the morphological findings, in which uni- and bilaterally lesioned animals did not differ significantly in the extent of TH-immunoreactive fiber and dopamine neuron loss within the nigrostriatal system in each lesioned hemisphere. These results indicate that the interdependent regulation of the two nigrostriatal systems may provide some compensatory support for the function and behavioral performance of the lesioned side viathe normal unlesioned side, which is lost in animals with bilateral lesions of the nigrostriatal system. Therefore, this model of uni- and bilateral partial lesions of the nigrostriatal system, as characterized in the present study, may foster further exploration of compensatory functional mechanisms active in the early stages of Parkinson's disease and promote development of novel neuroprotective and restorative strategies. J. Comp. Neurol. 432:217-229, 2001. (C) zool Wiley-Liss, Inc.

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Documento generato il 23/01/20 alle ore 06:33:18