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

• Published in: PloS one Vol. 12; no. 7; p. e0181677
• Main Authors: Napolitano, Francesco, Booth Warren, Emily, Migliarini, Sara, Punzo, Daniela, Errico, Francesco, Li, Qin, Thiolat, Marie-Laure, Vescovi, Angelo Luigi, Calabresi, Paolo, Bezard, Erwan, Morelli, Micaela, Konradi, Christine, Pasqualetti, Massimo, Usiello, Alessandro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.07.2017; Public Library of Science (PLoS)
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Adaptive systems; Aged; Aged, 80 and over; Animal models; Animal sciences; Animals; Biology and life sciences; Bipolar disorder; Bipolar Disorder - metabolism; Brain; Brain Chemistry - drug effects; Brain research; Case-Control Studies; Councils; Development and progression; Developmental biology; Disorders; Dopamine; Dopamine receptors; Dopaminergic mechanisms; Female; Gene expression; Genetic aspects; Genomes; GTP-binding protein; GTP-Binding Proteins - metabolism; Health aspects; Human performance; Humans; Innervation; Interneurons; Laboratory animals; Macaca mulatta; Male; Medicine; Medicine and Health Sciences; Mental disorders; Messenger RNA; Middle Aged; Monkeys & apes; Movement disorders; MPTP; Neostriatum; Neurodegenerative diseases; Neurological diseases; Neurons; Neurosciences; Neurotoxins; Neurotransmission; Parkinson disease; Parkinson Disease - metabolism; Parkinson's disease; Patients; Pharmaceutical sciences; Primates; Proteins; Putamen; Putamen - chemistry; Putamen - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Rodents; Schizophrenia; Schizophrenia - metabolism; Spiny neurons; Transcription; γ-Aminobutyric acid; Beijing China; United Kingdom > UK; United States > US; China; Italy; France; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181677

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.