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

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.

Xanthotoxin reverses Parkinson’s disease-like symptoms in zebrafish larvae and mice models: a comparative study

“…MPTP has been proved to be an important factor causing PD-like symptoms in both humans [ 25 ] and primates [ 26 ]. Repeated administration of MPTP causes the development of the parkinsonian features in mice [ 27 ].…”

Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age

“…In addition to its striatum (STR) enrichment [2,3,4,5,6], Rhes mRNA is also localised in cortical and midbrain regions of rodents and primates [7,8], and modulates striatal dopamine (DA) and adenosine-related signal transduction and behaviours [2,3,4,5,9], further confirming its modulatory role in psychiatric and neurological diseases in which DA is involved.…”

µ Opioid Receptor Agonism for L-DOPA-Induced Dyskinesia in Parkinson's Disease

“…Experiments were performed in accordance with the European Union directive of September 22, 2010 (2010/63/EU) on the protection of animals used for scientific purposes in an Association for Assessment and Accreditation of Laboratory Animal Care-accredited facility following acceptance of study design by the Institutional Animal Care and Use Committee of the Institute of Lab Animal Science (Chinese Academy of Science, Beijing, China). The tissues used in the present work were sourced from an experimental brain bank (females only) used on several previous occasions, the experimental conditions of which have been described previously in great details (Rylander et al, 2010;Santini et al, 2010;Shariatgorji et al, 2014;Engeln et al, 2015;Napolitano et al, 2017;Rojo-Bustamante et al, 2018;Mellone et al, 2019;Eshraghi et al, 2020). Briefly, macaque monkeys received daily MPTP hydrochloride injections (0.2 mg/kg, i.v.)…”