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Review
. 2014 Dec 15:8:155.
doi: 10.3389/fnana.2014.00155. eCollection 2014.

Parkinson's disease: animal models and dopaminergic cell vulnerability

Affiliations
Review

Parkinson's disease: animal models and dopaminergic cell vulnerability

Javier Blesa et al. Front Neuroanat. .

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that affects about 1.5% of the global population over 65 years of age. A hallmark feature of PD is the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and the consequent striatal DA deficiency. Yet, the pathogenesis of PD remains unclear. Despite tremendous growth in recent years in our knowledge of the molecular basis of PD and the molecular pathways of cell death, important questions remain, such as: (1) why are SNc cells especially vulnerable; (2) which mechanisms underlie progressive SNc cell loss; and (3) what do Lewy bodies or α-synuclein reveal about disease progression. Understanding the variable vulnerability of the dopaminergic neurons from the midbrain and the mechanisms whereby pathology becomes widespread are some of the primary objectives of research in PD. Animal models are the best tools to study the pathogenesis of PD. The identification of PD-related genes has led to the development of genetic PD models as an alternative to the classical toxin-based ones, but does the dopaminergic neuronal loss in actual animal models adequately recapitulate that of the human disease? The selection of a particular animal model is very important for the specific goals of the different experiments. In this review, we provide a summary of our current knowledge about the different in vivo models of PD that are used in relation to the vulnerability of the dopaminergic neurons in the midbrain in the pathogenesis of PD.

Keywords: 6-OHDA; ATP13A2; DJ1; LRRK2; MPTP; parkin; rotenone; synuclein.

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References

    1. Akundi R. S., Huang Z., Eason J., Pandya J. D., Zhi L., Cass W. A., et al. (2011). Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS ONE 6:e16038 10.1371/journal.pone.0016038 - DOI - PMC - PubMed
    1. Alam M., Mayerhofer A., Schmidt W. J. (2004). The neurobehavioral changes induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA. Behav. Brain Res. 151 117–124 10.1016/j.bbr.2003.08.014 - DOI - PubMed
    1. Andres-Mateos E., Mejias R., Sasaki M., Li X., Lin B. M., Biskup S., et al. (2009). Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). J. Neurosci. 29 15846–15850 10.1523/JNEUROSCI.4357-09.2009 - DOI - PMC - PubMed
    1. Andres-Mateos E., Perier C., Zhang L., Blanchard-Fillion B., Greco T. M., Thomas B., et al. (2007). DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc. Natl. Acad. Sci. U.S.A. 104 14807–14812 10.1073/pnas.0703219104 - DOI - PMC - PubMed
    1. Baiguera C., Alghisi M., Pinna A., Bellucci A., De Luca M. A., Frau L., et al. (2012). Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. Brain 135 2750–2765 10.1093/brain/aws193 - DOI - PMC - PubMed