Cellular and Molecular Life Sciences

, Volume 73, Issue 18, pp 3583–3597 | Cite as

Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson’s disease

  • Andrea Herrera
  • Patricia Muñoz
  • Irmgard Paris
  • Gabriela Díaz-Veliz
  • Sergio Mora
  • Jose Inzunza
  • Kjell Hultenby
  • Cesar Cardenas
  • Fabián Jaña
  • Rita Raisman-Vozari
  • Katia Gysling
  • Jorge Abarca
  • Harry W. M. Steinbusch
  • Juan Segura-AguilarEmail author
Original Article


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.


Preclinical model Dopamine, neurodegeneration Drugs Mitochondria Presynaptic vesicles 



This work was supported by FONDECYT # 1100165 (JSA), University of Chile ENL014/14 (JSA); ECOS-CONICYT # C10S02 (JSA, RR-V). FONDECYT # 1120443, FONDAP # 15150012 (CC) and FONDECYT postdoctoral fellowship # 3140458 (FJ)


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Andrea Herrera
    • 1
    • 8
  • Patricia Muñoz
    • 1
  • Irmgard Paris
    • 1
    • 3
  • Gabriela Díaz-Veliz
    • 1
  • Sergio Mora
    • 1
  • Jose Inzunza
    • 4
  • Kjell Hultenby
    • 5
  • Cesar Cardenas
    • 2
  • Fabián Jaña
    • 2
  • Rita Raisman-Vozari
    • 6
  • Katia Gysling
    • 7
  • Jorge Abarca
    • 7
  • Harry W. M. Steinbusch
    • 8
  • Juan Segura-Aguilar
    • 1
    Email author
  1. 1.Molecular and Clinical Pharmacology, ICBM, Faculty of MedicineUniversity of ChileSantiagoChile
  2. 2.Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Geroscience Center for Brain Health and Metabolism, SantiagoChile
  3. 3.Departamento de Ciencias BásicasUniversidad Santo TomasViña del MarChile
  4. 4.Department of Biosciences and NutritionKarolinska InstitutetStockholmSweden
  5. 5.Division of Clinical Research Center, Department of Laboratory MedicineKarolinska InstitutetStockholmSweden
  6. 6.INSERM U1127ParisFrance
  7. 7.Department of Cellular and Molecular Biology, Faculty of Biological SciencesPontificia Universidad Catolica de ChileSantiagoChile
  8. 8.Department of Translational Neuroscience, Faculty of Health, Medicine and Life SciencesMaastricht UniversityMaastrichtThe Netherlands

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