Pregled bibliografske jedinice broj: 458717
ERK phosphorilation and FosB expression are associated with the development of dyskinesia following L-DOPA treatment of hemiparkinsonian mice.
ERK phosphorilation and FosB expression are associated with the development of dyskinesia following L-DOPA treatment of hemiparkinsonian mice. // 11th Biennial European Behavioural Pharmacology Society Meeting
Barcelona, Španjolska, 2005. (poster, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 458717 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
ERK phosphorilation and FosB expression are associated with the development of dyskinesia following L-DOPA treatment of hemiparkinsonian mice.
Autori
Moratalla, Rosario ; Pavon, Nancy ; Mendialdua, Ainhoa ; Martín, Ana Belén, Darmopil, Sanja.
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Skup
11th Biennial European Behavioural Pharmacology Society Meeting
Mjesto i datum
Barcelona, Španjolska, 09.09.2005
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Dopamine; dynorphin; dyskinesia; ERK1/2 phosphorylation; FosB; Parkinson’s disease; striatum
Sažetak
The dopamine precursor 3, 4-dihydroxyphenyl-L-alanine (L-DOPA) is currently the most efficacious noninvasive therapy for Parkinson's disease. A major complication of this therapy, however, is the appearance of the abnormal involuntary movements known as dyskinesias. We have developed a model of L-DOPA-induced dyskinesias in mice that reproduces the main clinical features of dyskinesia in humans. Dyskinetic symptoms were triggered by repetitive administration of a constant dose of L-DOPA (25 mg/kg, twice a day, for 25 days) in unilaterally 6-hydroxydopamine (6-OHDA) lesioned mice. Mice were examined for behavior, expression of FosB, neuropeptides, and externally regulated kinase (ERK) phosphorylation. Dyskinetic symptoms appear toward the end of the first week of treatment and are associated with L-DOPA-induced changes in DeltaFosB and prodynorphin expression. L-DOPA also induces activation of ERK1/2 in the dopamine-depleted striatum. Interestingly, elevated FosB/DeltaFosB expression occurs exclusively within completely lesioned regions of the striatum, displaying an inverse correlation with remaining dopaminergic terminals. Following acute L-DOPA treatment, FosB expression occurs in direct striatal output neurons, whereas chronic L-DOPA also induces FosB expression in nitric oxide synthase-positive striatal interneurons. This model provides a system in which genetic manipulation of individual genes can be used to elucidate the molecular mechanisms responsible for the development and expression of dyskinesia.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Temeljne medicinske znanosti
