Early dysfunction of substantia nigra dopamine neurons in the parkinq311x mouse

Maria Regoni, Letizia Zanetti, Stefano Comai, Daniela Mercatelli, Salvatore Novello, Federica Albanese, Laura Croci, Gian Giacomo Consalez, Andrea Ciammola, Flavia Valtorta, Michele Morari, Jenny Sassone

Research output: Contribution to journalArticlepeer-review


Mutations in the PARK2 gene encoding the protein parkin cause autosomal recessive ju-venile parkinsonism (ARJP), a neurodegenerative disease characterized by early dysfunction and loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). No therapy is currently available to prevent or slow down the neurodegeneration in ARJP patients. Preclinical models are key to clarifying the early events that lead to neurodegeneration and reveal the potential of novel neuroprotective strategies. ParkinQ311X is a transgenic mouse model expressing in DA neurons a mutant parkin variant found in ARJP patients. This model was previously reported to show the neuropathological hallmark of the disease, i.e., the progressive loss of DA neurons. However, the early dysfunctions that precede neurodegeneration have never been investigated. Here, we ana-lyzed SNc DA neurons in parkinQ311X mice and found early features of mitochondrial dysfunction, extensive cytoplasmic vacuolization, and dysregulation of spontaneous in vivo firing activity. These data suggest that the parkinQ311X mouse recapitulates key features of ARJP and provides a useful tool for studying the neurodegenerative mechanisms underlying the human disease and for screening potential neuroprotective drugs.

Original languageEnglish
Article number514
Issue number5
Publication statusPublished - 2021


  • Cytoplasmic vacuolization
  • Dopaminergic neurons
  • Early dysfunction
  • Firing activity
  • Mitochondria
  • ParkinQ311X mouse
  • Parkinson’s disease

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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