Opposite modulation of regulators of G protein signalling-2 (RGS2) and RGS4 expression by dopamine receptors in the rat striatum

Geurts, Muriel; Hermans, Emmanuel; Maloteaux, J. M.

doi:10.1016/s0304-3940(02)01004-2

Cited by 43 publications

(23 citation statements)

References 19 publications

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“…274,275 RGS4 is involved in neuronal differentiation 276 and is under dopaminergic regulation. 277 Disrupted-in-schizophrenia 1 (DISC1) St Clair et al 278 described a large Scottish family in which a balanced translocation involving chromosomes 1 and 11 (1;11)(q42.1;q14.3) was strongly linked to psychopathology including schizophrenia, depression, and mania. The 1q breakpoint was cloned and found to involve two genes, called DISC1 and DISC2; the latter did not encode a protein, but may be an inhibitory RNA regulator of DISC1.…”

Section: Regulator Of G-protein Signalling 4 (Rgs4)mentioning

confidence: 99%

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

2004

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This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications. Molecular Psychiatry (2005) 10, 40-68.

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Section: Regulator Of G-protein Signalling 4 (Rgs4)mentioning

confidence: 99%

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

2004

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“…The mechanisms underlying this altered prefrontal cortical RGS4 expression in the PCP model of schizophrenia are unclear, but dopamine signaling may play a key role. Previous studies have shown that selective activation of dopamine D 2 receptors with specific agonists causes the upregulation of RGS4 expression in rat striatum (Geurts et al, 2002;Taymans et al, 2003). The functional deficit of dopamine neurotransmission in the prefrontal cortex in schizophrenia (Lewis and Lieberman, 2000) may cause the downregulation of RGS4 expression in PFC neurons.…”

Section: Discussionmentioning

confidence: 98%

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

Jiang²,

Yan³

2007

Mol Pharmacol

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Regulator of G protein signaling 4 (RGS4) has recently been identified as one of the genes linked to the susceptibility of schizophrenia. However, the functional roles of RGS4 and how it may be involved in the pathophysiology of schizophrenia remain largely unknown. In this study, we investigated the possible impact of RGS4 on the function of serotonin and dopamine receptors, two main targets for schizophrenia treatment. Activation of serotonin 5-HT 1A receptors or dopamine D 4 receptors down-regulates the function of NMDA receptor (NMDAR) channel, a key player controlling cognition and emotion, in pyramidal neurons of prefrontal cortex (PFC). Blocking RGS4 function significantly potentiated the 5-HT 1A regulation of NMDAR current; conversely, overexpression of RGS4 attenuated the 5-HT 1A effect. In contrast, the D 4 regulation of NMDAR current was not altered by RGS4 manipulation. Moreover, the 5-HT 1A regulation of NMDA receptors was significantly enhanced in a subset of PFC pyramidal neurons from rats treated with subchronic phencyclidine, an animal model of schizophrenia, which was found to be associated with specifically decreased RGS4 expression in these cells. Thus, our study has revealed an important coupling of RGS4 to serotonin signaling in cortical neurons and provided a molecular and cellular mechanism underlying the potential involvement of RGS4 in the pathophysiology of schizophrenia.

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“…RGS4 proteins can modulate G-protein-coupled receptor function in the brain (Zhong and Neubig, 2001;Hollinger and Hepler, 2002). Selective pharmacological stimulation of the DA D1 and D2 receptors has been shown to decrease and increase RGS4 expression in the striatum, respectively (Geurts et al, 2002;Taymans et al, 2003). Changes in RGS4 expression might thus be involved in alterations of signal transduction occurring after activation of D1 receptors by repeated cocaine stimulation.…”

Section: Receptors and Modulatorsmentioning

confidence: 99%

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

Zhang

Tang

et al. 2005

Neuropsychopharmacol

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Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca 2 þ /calmodulin-dependent protein kinase II a subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.

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Opposite modulation of regulators of G protein signalling-2 (RGS2) and RGS4 expression by dopamine receptors in the rat striatum

Cited by 43 publications

References 19 publications

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

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