Impaired dopamine release and synaptic plasticity in the striatum of Parkin-/- mice

Tohru Kitada, Antonio Pisani, Maha Karouani, Marian Haburcak, Giuseppina Martella, Anne Tscherter, Paola Platania, Bei Wu, Emmanuel N. Pothos, Jie Shen

Research output: Contribution to journalArticle

Abstract

Parkin is the most common causative gene of juvenile and early-onset familial Parkinson's diseases and is thought to function as an E3 ubiquitin ligase in the ubiquitin-proteasome system. However, it remains unclear how loss of Parkin protein causes dopaminergic dysfunction and nigral neurodegeneration. To investigate the pathogenic mechanism underlying these mutations, we used parkin-/- mice to study its physiological function in the nigrostriatal circuit. Amperometric recordings showed decreases in evoked dopamine release in acute striatal slices of parkin-/- mice and reductions in the total catecholamine release and quantal size in dissociated chromaffin cells derived from parkin-/- mice. Intracellular recordings of striatal medium spiny neurons revealed impairments of long-term depression and long-term potentiation in parkin-/- mice, whereas long-term potentiation was normal in the Schaeffer collateral pathway of the hippocampus. Levels of dopamine receptors and dopamine transporters were normal in the parkin-/- striatum. These results indicate that Parkin is involved in the regulation of evoked dopamine release and striatal synaptic plasticity in the nigrostriatal pathway, and suggest that impairment in evoked dopamine release may represent a common pathophysiological change in recessive parkinsonism.

Original languageEnglish
Pages (from-to)613-621
Number of pages9
JournalJournal of Neurochemistry
Volume110
Issue number2
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Dopamine transporter
  • Dopaminergic
  • Knockout
  • Mouse

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Kitada, T., Pisani, A., Karouani, M., Haburcak, M., Martella, G., Tscherter, A., Platania, P., Wu, B., Pothos, E. N., & Shen, J. (2009). Impaired dopamine release and synaptic plasticity in the striatum of Parkin-/- mice. Journal of Neurochemistry, 110(2), 613-621. https://doi.org/10.1111/j.1471-4159.2009.06152.x