A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice

Vincenza D'Angelo, Mauro Giorgi, Emanuela Paldino, Silvia Cardarelli, Francesca R Fusco, Ilaria Saverioni, Roberto Sorge, Giuseppina Martella, Stefano Biagioni, Nicola B Mercuri, Antonio Pisani, Giuseppe Sancesario

Research output: Contribution to journalArticlepeer-review

Abstract

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/- knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+/+, immunofluorescence showed A2A roundish aggregates, 0.3-0.4 μm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+/-, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+/-, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+/+. Finally, in Tor1a+/-, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+/-, opposite changes of A2A receptors' expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.

Original languageEnglish
JournalInt J Mol Sci
Volume22
Issue number5
DOIs
Publication statusPublished - Mar 7 2021

Keywords

  • Animals
  • Basal Ganglia/metabolism
  • Cholinergic Neurons/metabolism
  • Corpus Striatum/metabolism
  • Cyclic AMP/metabolism
  • Disease Models, Animal
  • Dystonia Musculorum Deformans/genetics
  • Gene Expression Regulation
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Molecular Chaperones/genetics
  • RNA, Messenger
  • Receptor, Adenosine A2A/genetics

Fingerprint

Dive into the research topics of 'A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice'. Together they form a unique fingerprint.

Cite this