Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons

Sciamanna, Giuseppe; Napolitano, Francesco; Pelosi, Barbara; Bonsi, Paola; Vitucci, Daniela; Nuzzo, Tommaso; Punzo, Daniela; Ghiglieri, Veronica; Ponterio, Giulia; Pasqualetti, Massimo; Pisani, Antonio; Usiello, Alessandro

doi:10.1016/j.nbd.2015.03.021

Cited by 25 publications

(36 citation statements)

References 60 publications

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“…Considering the pivotal role of DA system in regulating PPI response (Braff et al, 2001), and coherently with an involvement of Rasd2 in the modulation of this neurotransmission (Errico et al, 2008;Harrison and LaHoste, 2006;Sciamanna et al, 2015), our behavioral data indicate that targeted deletion of this gene induces significant sensorimotor gating deficits in naïve male mutants. Moreover, we also documented that administration of both Amph and PCP triggers prominent PPI deficits in mutants, when compared with their matched-treated controls.…”

Section: Rasd2 Regulates Psychotomimetic Drug Effects D Vitucci Et Alsupporting

confidence: 72%

“…Consistently, targeted deletion of this gene in mice results in increased striatal cAMP/PKA signaling (Errico et al, 2008;Ghiglieri et al, 2015). Besides its well-established expression within striatal GABAergic medium spiny-projecting neurons, we recently demonstrated that Rasd2 is also virtually localized in all cholinergic interneurons in humans and mice, where it affects DA D2R-dependent firing activity and signaling (Sciamanna et al, 2015). On the other hand, Rasd2 is able to modulate AKT and mTOR signaling cascades Subramaniam et al, 2012), well known to be involved in neurological (Lee et al, 2015) and psychiatric disorders (Emamian et al, 2004).…”

Section: Introductionmentioning

confidence: 56%

“…Rasd2 encodes for a small GTP-binding protein highly expressed in the striatum and nucleus accumbens of rodents (Errico et al, 2008;Vargiu et al, 2004), where it affects neuronal processes associated with cAMP/PKA and AKT signaling transduction cascades (Ghiglieri et al, 2015;Harrison and Lahoste, 2013). Furthermore, Rasd2 also influences DA D1R-and D2R-related processes within striatal GABAergic projection neurons and cholinergic interneurons (Errico et al, 2008;Ghiglieri et al, 2015;Sciamanna et al, 2015). On the other hand, recent studies have suggested that Rasd2, through SUMO and mTOR pathway regulation, has a pivotal role in the genesis of neurological disorders involving the striatum, such as Huntington's disease (Lee et al, 2015;Subramaniam et al, 2010) and L-DOPA-induced dyskinesia (Subramaniam et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Ten-to-12-week-old male and female wild-type (WT) and Rasd2 knockout (KO) mice without PGK-neo cassette (Ghiglieri et al, 2015;Sciamanna et al, 2015), derived from mating of heterozygous animals (Rasd2 +/ − ), backcrossed to F11 generation to C57BL/6J strain, were used in this study. Mice were housed in groups in standard cages (29 × 17.5 × 12.5 cm 3 ) at constant temperature (22 ± 1°C) and maintained on a 12/12 h light/dark cycle, with food and water ad libitum.…”

Section: Animal Methodsmentioning

confidence: 99%

“…ISH analysis was performed according to protocols previously described (Sciamanna et al, 2015). Mouse fresh brain tissue was embedded in Tissue Tek (Sakura) and frozen at − 80°C, and 14-μm cryostat sections were cut in the coronal plane.…”

Section: In Situ Hybridization (Ish)mentioning

confidence: 99%

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Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

Vitucci

Giorgio

Napolitano

et al. 2015

Neuropsychopharmacol

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Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

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Section: Rasd2 Regulates Psychotomimetic Drug Effects D Vitucci Et Alsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Animal Methodsmentioning

confidence: 99%

Section: In Situ Hybridization (Ish)mentioning

confidence: 99%

See 3 more Smart Citations

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

Vitucci

Giorgio

Napolitano

et al. 2015

Neuropsychopharmacol

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Rhes Tunnels: A Radical New Way of Communication in the Brain's Striatum?

Subramaniam

2020

BioEssays

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Ras homolog enriched in the striatum (Rhes) is a striatal enriched protein that promotes the formation of thin membranous tubes resembling tunneling nanotubes (TNT)-"Rhes tunnels"-that connect neighboring cell and transport cargoes: vesicles and proteins between the neuronal cells. Here the literature on TNT-like structures is reviewed, and the implications of Rhes-mediated TNT, the mechanisms of its formation, and its potential in novel cell-to-cell communication in regulating striatal biology and disease are emphasized. Thought-provoking ideas regarding how Rhes-mediated TNT, if it exists, in vivo, would radically change the way neurons communicate in the brain are discussed.

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Probing striatal microcircuitry to understand the functional role of cholinergic interneurons

Girasole

Nelson

2015

Movement Disorders

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Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons

Cited by 25 publications

References 60 publications

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

Rhes Tunnels: A Radical New Way of Communication in the Brain's Striatum?

Probing striatal microcircuitry to understand the functional role of cholinergic interneurons

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