Intrastriatal botulinum toxin abolishes pathologic rotational behaviour and induces axonal varicosities in the 6-OHDA rat model of Parkinson's disease.
Neurobiol Dis
; 41(2): 291-8, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-20955797
ABSTRACT
Central pathophysiological pathways of basal ganglia dysfunction imply a disturbed interaction of dopaminergic and cholinergic circuits. In Parkinson's disease (PD) imbalanced cholinergic hyperactivity prevails in the striatum. Interruption of acetylcholine (ACh) release in the striatum by locally injected botulinum neurotoxin A (BoNT-A) has been studied in the rat 6-hydroxydopamine (6-OHDA) model of PD (hemi-PD). The hemi-PD was induced by injection of 6-OHDA into the right medial forebrain bundle. Motor dysfunction provoked by apomorphine-induced contralateral rotation was completely reversed for more than 3 months by ipsilateral intrastriatal application of 1-2 ng BoNT-A. Interestingly, BoNT-A injected alone into the right striatum of naïve rats caused a slight transient ipsilateral apomorphine-induced rotation, which lasted only for about one month. Immunohistochemically, large axonal swellings appeared within the striatum injected with BoNT-A, which we tentatively named BoNT-A-induced varicosities. They contained either choline acetyltransferase or tyrosine hydroxylase. These findings suggest a selective inhibition of evoked release of ACh by locally applied BoNT-A. Intrastriatal application of BoNT-A may antagonize localized relative functional disinhibited hypercholinergic activity in neurodegenerative diseases such as PD avoiding side effects of systemic anti-cholinergic treatment.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rotación
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Axones
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Oxidopamina
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Toxinas Botulínicas Tipo A
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Cuerpo Estriado
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Trastornos Parkinsonianos
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Regeneración Nerviosa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania