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Dopaminergic Neuron-Specific Autophagy-Deficient Mice

Protocol
Part of the Methods in Molecular Biology book series

Abstract

None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.

Keywords

Atg7 Autophagy Dopaminergic neuron Lewy body Mouse model Parkinson’s disease 

References

  1. 1.
    Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC (2003) Alpha-synuclein is degraded by both autophagy and the proteasome. J Biol Chem 278:25009–25013Google Scholar
  2. 2.
    Spencer B et al (2009) Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson’s and Lewy body diseases. J Neurosci 29:13578–13588Google Scholar
  3. 3.
    Yu WH et al (2009) Metabolic activity determines efficacy of macroautophagic clearance of pathological oligomeric alpha-synuclein. Am J Pathol 175:736–747Google Scholar
  4. 4.
    Hara T et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889Google Scholar
  5. 5.
    Komatsu M et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–884Google Scholar
  6. 6.
    Friedman LG et al (2012) Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of alpha-synuclein and LRRK2 in the brain. J Neurosci 32:7585–7593Google Scholar
  7. 7.
    Sato S et al (2018) Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice. Sci Rep 8:2813Google Scholar

Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  1. 1.Department of NeurologyJuntendo University Graduate School of MedicineTokyoJapan

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