Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques

Paolo Calabresi, Francesco Napolitano, Emily Booth Warren, Sara Migliarini, Daniela Punzo, Francesco Errico, Qin Li, Marie-Laure Thiolat, Angelo Luigi Vescovi, Erwan Bezard, Micaela Morelli, Christine Konradi, Massimo Pasqualetti, Alessandro Usiello

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson’s disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.
Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalPLoS One
Volume12
DOIs
Publication statusPublished - 2017

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Aged
  • Aged, 80 and over
  • Animals
  • Bipolar Disorder
  • Brain Chemistry
  • Case-Control Studies
  • Female
  • GTP-Binding Proteins
  • Humans
  • Macaca mulatta
  • Male
  • Middle Aged
  • Parkinson Disease
  • Putamen
  • RNA, Messenger
  • Schizophrenia

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