Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson’s disease
Author
dc.contributor.author
Herrera, Andrea
Author
dc.contributor.author
Muñoz Tapia, Patricia
Author
dc.contributor.author
Paris Pizarro, Irmgard
Author
dc.contributor.author
Díaz Véliz, Gabriela
Author
dc.contributor.author
Mora Gutiérrez, Sergio
Author
dc.contributor.author
Inzunza, José
Author
dc.contributor.author
Hultenby, Kjell
Author
dc.contributor.author
Cárdenas Matus, Julio
Author
dc.contributor.author
Jaña Prado, Fabián
Author
dc.contributor.author
Raisman Vozari, Rita
Author
dc.contributor.author
Gysling, Katia
Author
dc.contributor.author
Abarca, Jorge
Author
dc.contributor.author
Steinbusch, Harry
Author
dc.contributor.author
Segura Aguilar, Juan
Admission date
dc.date.accessioned
2017-01-04T20:27:35Z
Available date
dc.date.available
2017-01-04T20:27:35Z
Publication date
dc.date.issued
2016
Cita de ítem
dc.identifier.citation
Cell. Mol. Life Sci. (2016) 73:3583–3597
es_ES
Identifier
dc.identifier.other
10.1007/s00018-016-2182-5
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/142262
Abstract
dc.description.abstract
L-Dopa continues to be the gold drug in Parkinson's disease ( PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in ( 1) contralateral rotation when the animals are stimulated with apomorphine; ( 2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; ( 3) cell shrinkage; ( 4) significant reduction of dopamine release; ( 5) significant increase in GABA release; ( 6) significant decrease in the number of monoaminergic presynaptic vesicles; ( 7) significant increase of dopamine concentration inside of monoaminergic vesicles; ( 8) significant increase of damaged mitochondria; ( 9) significant decrease of ATP level in the striatum ( 10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease
es_ES
Patrocinador
dc.description.sponsorship
FONDECYT 1100165 1120443 3140458
University of Chile ENL014/14
ECOS-CONICYT C10S02
FONDAP 15150012