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
Article number2691
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume22
Issue number5
DOIs
Publication statusPublished - Mar 1 2021

Keywords

  • A2A
  • A2A mRNA
  • Basal ganglia
  • CAMP
  • D2
  • Dystonia
  • DYT1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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