Modulation of striatal cAMP levels: a paradigm shift in the treatment of hyperkinetic movement disorders
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE298638 | GEO | 2025/06/13
REPOSITORIES: GEO
Similar Datasets
Project description:Modulation of striatal cAMP levels: a paradigm shift in the treatment of hyperkinetic movement disorders
| PRJNA1271045 | ENA
Project description:Fungal degradation of lignocellulosic biomass requires various (hemi-)cellulases and plays key roles in biological carbon cycle. Although cellulases induction recently described in some saprobic filamentous fungi, regulation of cellulase transcription has not been studied thoroughly. Here, we identified and characterized the novel cellulase regulation factors clr-4 in Neurospora crassa and its ortholog Mtclr-4 in Myceliophthora thermophila. Deletion of clr-4 and Mtclr-4 displayed similarly defective phenotypes in cellulolytic enzymes production and activities. Transcriptomics analysis of Δclr-4/ΔMtclr-4 revealed down-regulation of not only encoding genes of (hemi-)cellulases and pivotal regulators (clr-1, clr-2 and xyr-1), but also the key genes of cAMP signaling pathway such as adenylate cyclase cr-1. Consistently, the significant decreased levels of intracellular cAMP were observed in Δclr-4/ΔMtclr-4 compared to wild-type during cellulose utilization. Electrophoretic mobility shift assays (EMSA) verified that CLR-4 could directly bind to the promoter regions of adenylyl cyclase (Nccr-1) and cellulose regulator clr-1, while MtCLR-4 bind to upstream regions of adenylyl cyclase Mtcr-1 and biomass deconstruction regulators Mtclr-2 and Mtxyr-1. Concluded, the novel cellulase expression regulators (CLR-4/MtCLR-4) findings here significantly enrich our understanding of the regulatory network of cellulose degradation and provide new targets for industrial fungi strain engineering for plant biomass deconstruction in biorefinery.
2021-03-18 | GSE111986 | GEO
Project description:The whooping cough agent, Bordetella pertussis, subverts dendritic cell (DCs) functions through powerful immunomodulatory activities of its toxins. Here we focused on the signaling action of the adenylate cyclase toxin (CyaA) that targets myeloid cells expressing the αMβ2 integrin CD11b/CD18 (known as complement receptor 3 (CR3) or Mac-1). CyaA delivers an extremely catalytically potent adenylyl cyclase enzyme domain into the cytosol of phagocytes and disrupts their innate and adaptive immune functions through unregulated production of the key signaling molecule cAMP. Here we describe the global phosphoproteomic analysis of cAMP signaling in murine bone marrow-derived DCs exposed to CyaA. Gathered data reveal toxin-triggered alternations of phosphorylation status of proteins regulating actin cytoskeleton, chromatin remodeling, mTOR activity and IL-10 gene expression. The reported findings highlight the complexity of subversive physiological manipulation that is exerted on myeloid phagocytes by the cAMP-generating adenylate cyclase toxin of Bordetellae.
2017-11-29 | PXD004733 | Pride
Project description:Nociceptive neuropeptide CGRP acts directly on HSCs via the its receptor RAMP1/CALCRL, to promote egress by activating Gαs/Adenylyl cyclase/cAMP pathway.
2020-10-12 | GSE156449 | GEO
Project description:The cAMP-pathway plays a central role in regulation of growth, differentiation, and virulence of human pathogenic fungi, including Cryptococcus neoformans. Three major upstream signaling regulators of the adenylyl cyclase (Cac1), Ras, Aca1 (Adenylyl cyclase-associated protein 1) and G-alpha subunit protein (Gpa1), have been identified to control the cAMP-pathway in C. neoformans, but their functional relationship remains elusive. Here we performed genome-wide transcriptome analysis with C. neoformans ras1, gpa1, cac1, aca1, and pka1 pka2 mutants by DNA microarray. The aca1, gpa1, cac1, and pka1 pka2 mutants displayed similar transcriptome patterns to each other whereas the ras1 mutant exhibited distinctive transcriptome patterns compared to WT and the cAMP mutants. Interestingly, a number of environmental stress response genes are differentially modulated in the ras1 and cAMP mutants. In fact, the Ras1-signaling pathway was found to be involved in osmotic and genotoxic stress response, and maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Through this microarray analysis, we have identified a number of cAMP-dependent genes, including GRE2, HSP12, ENA1, TCO2, PKP2, CAT1, in C. neoformans. Notably, a majority of ergosterol biosynthesis genes were found to be upregulated in the cAMP mutants. Interestingly, the gpa1, cac1, and pka1 mutants, but not the aca1 and pka2 mutants were hypersensitive to amphotericin B, but resistant to fluconazole. In conclusion, we demonstrated in this study that the Ras1- and cAMP-signaling pathways are involved in stress response and sterol biosynthesis of C. neoformans.
2009-09-26 | GSE17338 | GEO
Project description:Human neuroimaging studies of reward processing typically involve tasks that engage decision-making processes in the dorsal striatum or focus upon the ventral striatum's response to feedback expectancy. These studies are often compared to the animal literature; however, some animal studies include both feedback and nonfeedback events that activate the dorsal striatum during feedback expectancy. Differences in task parameters, movement complexity, and motoric effort to attain rewards may partly explain ventral and dorsal striatal response differences across species. We, therefore, used a target capture task during functional neuroimaging that was inspired by a study of single cell modulation in the internal globus pallidus during reward-cued, rotational arm movements in nonhuman primates. In this functional magnetic resonance imaging study, participants used a fiberoptic joystick to make a rotational response to an instruction stimulus that indicated both a target location for a capture movement and whether or not the trial would end with feedback indicating either a small financial gain or a neutral outcome. Portions of the dorsal striatum and pallidum demonstrated greater neural activation to visual cues predicting potential gains relative to cues with no associated outcome. Furthermore, both striatal and pallidal regions displayed a greater response to financial gains relative to neutral outcomes. This reward-dependent modulation of dorsal striatal and pallidal activation in a target-capture task is consistent with findings from reward studies in animals, supporting the use of motorically complex tasks as translational paradigms to investigate the neural substrates of reward expectancy and outcome in humans.
| S-EPMC4668805 | biostudies-literature
Project description:The cAMP-pathway plays a central role in regulation of growth, differentiation, and virulence of human pathogenic fungi, including Cryptococcus neoformans. Three major upstream signaling regulators of the adenylyl cyclase (Cac1), Ras, Aca1 (Adenylyl cyclase-associated protein 1) and G-alpha subunit protein (Gpa1), have been identified to control the cAMP-pathway in C. neoformans, but their functional relationship remains elusive. Here we performed genome-wide transcriptome analysis with C. neoformans ras1, gpa1, cac1, aca1, and pka1 pka2 mutants by DNA microarray. The aca1, gpa1, cac1, and pka1 pka2 mutants displayed similar transcriptome patterns to each other whereas the ras1 mutant exhibited distinctive transcriptome patterns compared to WT and the cAMP mutants. Interestingly, a number of environmental stress response genes are differentially modulated in the ras1 and cAMP mutants. In fact, the Ras1-signaling pathway was found to be involved in osmotic and genotoxic stress response, and maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Through this microarray analysis, we have identified a number of cAMP-dependent genes, including GRE2, HSP12, ENA1, TCO2, PKP2, CAT1, in C. neoformans. Notably, a majority of ergosterol biosynthesis genes were found to be upregulated in the cAMP mutants. Interestingly, the gpa1, cac1, and pka1 mutants, but not the aca1 and pka2 mutants were hypersensitive to amphotericin B, but resistant to fluconazole. In conclusion, we demonstrated in this study that the Ras1- and cAMP-signaling pathways are involved in stress response and sterol biosynthesis of C. neoformans. There are more than 95% of genome homology between JEC21 and H99. Therefore 100 slides of JEC21 (cryptococcus neoformans var. neoformans serotype D) 70-mer oligo are used in this analysis, 3 biological replicate experiments are performed, total RNAs are extracted with 6 strains from H99 (H99 Wild type strain (Cryptococcus neoformans var. grubii serotype A), ras1Î, aca1Î, gpa1Î, cac1Î, pka1Îpka2Î), We use the mixed all of total RNAs from this experiment as a control RNA. We use Cy5 as Sample dye and Cy3 as a control dye. several sample are dye swaped.
2010-05-22 | E-GEOD-17338 | biostudies-arrayexpress
Project description:The aim of this experiment was to absolutely quantify adenylyl cyclase 8 (AC8) and the co-purified interactor calmodulin (CaM) to assess their stoichiometry.
2024-02-14 | PXD044766 | Pride
Project description:Abstract The surprising outbreak of an anticipated virus has exposed that the profit?centered mode of production renders a dysfunctional society, with a high incidence of pandemic?prone diseases. Consequently, the global health crisis and subsequent economic collapse threatening the existence of billions reveal the ultimate market failure from both heterodox and radical theoretical viewpoints. The demise of markets and capitalist systems calls for a straightforward economic intervention and radical transformation of the way societal production is conceptualized. This paradigm shift must deprioritize economic growth driven by the omnipresent commodification of all social relations and must furnish a viable alternative provided by the political economy. The starting point for such fundamental change in the dominant discourse must be rooted in balancing between the needs and wants, and in creating an environment in which properly understood self?interest would bring about a sustainable and equitable increase in societal well?being.
| S-EPMC7436549 | biostudies-literature
Project description:MicroRNAs (miRNAs) regulate many basic aspects of cell biology including neuronal plasticity, but little is known of their roles in drug addiction. Extended access to cocaine can trigger the emergence of compulsive drug-seeking behaviors, but molecular mechanisms regulating this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with extended access to cocaine. Striatal overexpression of miR-212 decreases, whereas its inhibition increases cocaine intake in rats with extended but not restricted drug access, suggesting that miR-212 serves as a protective factor against the development of compulsive drug seeking. The transcription factor CREB (cAMP response element-binding protein) is considered a core regulator of cocaine reward. We show that miR-212 controls responsiveness to cocaine by dramatically amplifying striatal CREB signaling. This action occurs through miR-212-enhanced Raf-1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (Transducer of Regulated CREB; also known as CRTC). Our findings suggest that striatal miR-212 signaling plays a key role in vulnerability to addiction, and that noncoding RNAs such as the miRNAs may serve as novel targets for the development of anti-addiction therapeutics. To identify potential targets for miR-212, we transfected cells with a vector to overexpress miR-212 or an empty vector. We then analyzed profiled gene expression using Affymetrix arrays.
2010-07-08 | GSE21901 | GEO