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PLoS One. 2017 Jul 25;12(7):e0181677. doi: 10.1371/journal.pone.0181677. eCollection 2017.

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

Author information

Ceinge Biotecnologie Avanzate, Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Department of Pharmacology, Vanderbilt University, Nashville, TN, United States of America.
Department of Biology Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Italy.
Motac Neuroscience, UK-M15 6WE, Manchester, United Kingdom.
Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.
Université de Bordeaux, Institut des Maladies Neurodégénératives,Bordeaux, France.
Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France.
IRCSS Casa Sollievo della Sofferenza, ISBReMIT-Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies, San Giovanni Rotondo, Italy.
Department of Medicine, University of Perugia and Clinica Neurologica, Santa Maria della Misericordia Hospital, Perugia, Italy.
National Research Council of Italy (CNR), Neuroscience Institute, Cagliari, Italy.
Department of Biomedical Sciences, section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy.
Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, TN, Italy.
Neuroscience Institute, National Research Council (CNR), Pisa, Italy.


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.

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