The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons

Errico, Francesco; Santini, Emanuela; Migliarini, Sara; Borgkvist, Anders; Centonze, Diego; Nasti, Valentina; Carta, Manolo; Chiara, Valentina De; Prosperetti, Chiara; Spano, Daniela; Hervé, Denis; Pasqualetti, Massimo; Lauro, Roberto Di; Fisone, Gilberto; Usiello, Alessandro

doi:10.1016/j.mcn.2007.10.007

Cited by 72 publications

(121 citation statements)

References 42 publications

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“…Rasd2 is known to be regulated by thyroid hormones (Errico et al 2008) and interestingly we found the expression of its potential downstream target-Amigo2-to be highly correlated with total serum thyroxine (r ¼ 0.87, P , 0.005; trait ID, 10602). The expression of Amigo2 was shown to promote the survival of cerebellar granule neurons and was considered a candidate for familial Alzheimer's disease type 5 (Ono et al 2003).…”

Section: Resultsmentioning

confidence: 61%

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Ciobanu

Mozhui

et al. 2010

Genetics

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Common sequence variants within a gene often generate important differences in expression of corresponding mRNAs. This high level of local (allelic) control-or cis modulation-rivals that produced by gene targeting, but expression is titrated finely over a range of levels. We are interested in exploiting this allelic variation to study gene function and downstream consequences of differences in expression dosage. We have used several bioinformatics and molecular approaches to estimate error rates in the discovery of cis modulation and to analyze some of the biological and technical confounds that contribute to the variation in gene expression profiling. Our analysis of SNPs and alternative transcripts, combined with eQTL maps and selective gene resequencing, revealed that between 17 and 25% of apparent cis modulation is caused by SNPs that overlap probes rather than by genuine quantitative differences in mRNA levels. This estimate climbs to 40-50% when qualitative differences between isoform variants are included. We have developed an analytical approach to filter differences in expression and improve the yield of genuine cis-modulated transcripts to $80%. This improvement is important because the resulting variation can be successfully used to study downstream consequences of altered expression on higherorder phenotypes. Using a systems genetics approach we show that two validated cis-modulated genes, Stk25 and Rasd2, are likely to control expression of downstream targets and affect disease susceptibility.

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Section: Resultsmentioning

confidence: 61%

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Ciobanu

Mozhui

et al. 2010

Genetics

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“…This protocol was performed as reported previously (Errico et al, 2008;De Chiara et al, 2010). In brief, mice were placed into the center of a clear Plexiglas arena (25 ϫ 35 ϫ 20 cm) in which they were allowed to explore for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates with the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition

et al. 2010

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The endocannabinoid anandamide (AEA) plays a crucial role in emotional control, and inhibition of its degradation by the fatty acid amide hydrolase (FAAH) has a potent antianxiety effect. The mechanism by which the magnification of AEA activity reduces anxiety is still largely undetermined. By using FAAH mutant mice and both intraperitoneal and intracerebroventricular administration of the FAAH inhibitor (3Ј-(aminocarbonyl)[1,1Ј-biphenyl]-3-yl)-cyclohexylcarbamate (URB597), we found that enhanced AEA signaling reversed, via central cannabinoid CB1 receptors (CB1Rs), the anxious phenotype of mice exposed to social defeat stress. This behavioral effect was associated with preserved activity of CB1Rs regulating GABA transmission in the striatum, whereas these receptors were dramatically down-regulated by stress in control animals. The hypothalamic-pituitaryadrenal (HPA) axis was not involved in the antistress effects of FAAH inhibition, although the HPA axis is a biological target of endogenous AEA. We also provided some physiological indications that striatal CB1Rs regulating GABA synapses are not the receptor targets of FAAH inhibition, which rather resulted in the stimulation of striatal CB1Rs regulating glutamate transmission. Collectively, our findings suggest that preservation of cannabinoid CB1 receptor function within the striatum is a possible synaptic correlate of the antianxiety effects of FAAH inhibition.The lifespan of the endocannabinoid anandamide (AEA) is regulated by the fatty acid amide hydrolase (FAAH), which cleaves and increases tissue levels of AEA (Kathuria et al., 2003;McKinney and Cravatt, 2005;. Enhancement of AEA signaling through FAAH inhibition has emerged recently as an interesting novel route in the treatment of mood disorders (Kathuria et al.,

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“…To evaluate balance, motor coordination, and motor learning, DAT-CI (n ϭ 14) and WT (n ϭ 15) naive mice were tested on the accelerating rotarod (Ugo Basile; Biological Research Apparatus), as previously described (Errico et al, 2008). The test was performed by placing mice on a rotating drum (3 cm of diameter) and measuring the time that each mouse was able to achieve walking on the top of the rod.…”

Section: Behaviormentioning

confidence: 99%

Role of Aberrant Striatal Dopamine D₁Receptor/cAMP/Protein Kinase A/DARPP32 Signaling in the Paradoxical Calming Effect of Amphetamine

Napolitano¹,

Bonito‐Oliva²,

Federici³

et al. 2010

J. Neurosci.

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The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons

Cited by 72 publications

References 42 publications

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates with the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition

Role of Aberrant Striatal Dopamine D₁Receptor/cAMP/Protein Kinase A/DARPP32 Signaling in the Paradoxical Calming Effect of Amphetamine

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The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons

Cited by 72 publications

References 42 publications

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates with the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition

Role of Aberrant Striatal Dopamine D1Receptor/cAMP/Protein Kinase A/DARPP32 Signaling in the Paradoxical Calming Effect of Amphetamine

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Role of Aberrant Striatal Dopamine D₁Receptor/cAMP/Protein Kinase A/DARPP32 Signaling in the Paradoxical Calming Effect of Amphetamine