Microarray analysis of WT and Drd2-/- striatal tissue from C57BL/6 mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE41638 | GEO | 2012/10/25
SECONDARY ACCESSION(S): PRJNA177789
REPOSITORIES: GEO
Similar Datasets
Project description:Drd2 regulates striatal gene networks. WT and KO striatal tissue were dissected from 2-month-old naïve male C57BL/6 genetic background mice and subjected to microarray analysis.
2012-10-25 | E-GEOD-41638 | biostudies-arrayexpress
Project description:We performed a study of gene expression changes that occur during mouse aging in the striatum and cortex in specific neuronal populations. Using translating ribosome afifnity purificaiton, we captured cell type-specific mRNAs from Drd1a-expressing cortical neurons, Drd1a-expressing striatal neurons, Drd2-expressing cortical neurons, and Drd2-expressing striatal neurons. 31 total samples were anlayzed. We generated the followinf pairwise comparisons: Old (2 years) vs young (6 weeks) Drd1a expressing cortical cells; old (2 years) vs young (6 weeks) Drd2 expressing cortical cells; old (2 years) vs young (6 weeks) Drd1a expressing striatal cells; old (2 years) vs young (6 weeks) Drd2 expressing striatal cells. We used a restriction of Benjamini-Hochberg FDR <0.05, and a fold-change restriction of 1.2-fold.
2014-12-13 | E-GEOD-64140 | biostudies-arrayexpress
Project description:We performed a study of gene expression changes that occur during mouse aging in the striatum and cortex in specific neuronal populations. Using translating ribosome afifnity purificaiton, we captured cell type-specific mRNAs from Drd1a-expressing cortical neurons, Drd1a-expressing striatal neurons, Drd2-expressing cortical neurons, and Drd2-expressing striatal neurons.
2014-12-13 | GSE64140 | GEO
Project description:Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and non-canonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and inflammation which are highly correlated with the amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking Drd2 in neurons. Together, our findings reveal previously uncharted roles for a DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.
2022-07-15 | GSE205290 | GEO
Project description:Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and non-canonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and inflammation which are highly correlated with the amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking Drd2 in neurons. Together, our findings reveal previously uncharted roles for a DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.
2022-07-15 | GSE205291 | GEO
Project description:L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. To profile the cell-type-specific responses of striatal spiny projection neurons (SPNs) to striatal dopamine depletion, we conducted TRAP analysis of the two major classes of these neurons: dSPNs that express the dopamine receptor 1a (Drd1a), and iSPNs that express the dopamine receptor 2 (Drd2). To disrupt dopamine innervation to both of these SPN populations that reside in the striatum, we injected the neurotoxin 6-hydroxydopamine (6-OHDA), unilaterally, in the medial forebrain bundle (MFB) in hemizygous Drd1-TRAP and Drd2-TRAP adult (9-14 weeks) male mice (kept on a C57BL/6J genetic background). This lesion procedure causes nigral dopamine cell death within a few days, along with a widespread and near-complete loss of dopaminergic innervation to the entire dorsal striatum on one side of the brain (a hemiparkinsonian model). We first examined the effects of dopamine depletion alone, compared to a mock lesion (ascorbate / saline injected). We then examined the effects of chronic levodopa treatment upon the molecular profiles of dopamine- depleted dSPNs and iSPNs, with two dose regimens. The ‘high-dose’ L-DOPA regimen (3 mg/kg on days 1-3, followed by 6 mg/kg on days 4-9) was expected to induce severe dyskinesia in all MFB-lesioned mice. The low-dose L-DOPA regimen (1 mg/kg on days 1-3, followed by 2 mg/kg on days 4-9) was expected to reverse limb use asymmetry without causing conspicuous dyskinesias. To equalize the effects of stress and handling across all groups, including control groups, all mice were equally handled and thus received saline injections when not receiving levodopa injections. Each treatment group contained 7-10 replicates. TRAP-purified mRNAs from either Drd1a- or Drd2-expressing SPNs were reverse-transcribed, amplified, and used to interrogate Affymetrix 430_2.0 GeneChip microarrays.
2014-03-03 | E-GEOD-55096 | biostudies-arrayexpress
Project description:The heterogeneity of cortical dopamine D2 receptor expressing cells is not well characterized We performed microarrays to study expression of all the transcriprts specifically from Drd2+ neurons of mouse mPFC. For this we immunoprecipitated ribosomes from mPFC of D2Cre::RiboTag mouse, where ribosomal subunit Rpl22 is tagged with HA epitope specifically in Drd2+ neurons
2018-06-16 | GSE115887 | GEO
Project description:DRD2 agonists are effective in treating pituitary tumors. To fathom the β-arresin-dependent mechanisms underlying DRD2-mediated pituitary tumor growth suppression,we applied RNA-seq analysis to rat pituitary MMQ cells treated with a DRD2 β-arresin-biased agoinst, UNC9994.MMQ cells were treated with UNC9994(15μM) or vehecle control for 12 h or 24 h and then subject to RNA-seq analysis.We found oxidative-stress-related genes such as Nqo1 and Hmox1 were upregulated by UNC9994, revealing oxidative stress may be the basis of UNC9994-induced tumor growth suppression. Our study represents the first detailed analysis of transcriptomes in rat pituitary MMQ cells treated with DRD2 β-arresin-biased agonist.The significance of altered expression of specific transcripts will enhance our understanding of DRD2 signaling in pituitary tumor cells.
2023-07-13 | GSE154351 | GEO
Project description:Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice. For microarray analysis, hippocampus, hypothalamus, cortex and striatum of Camk2a-Cre; GLPfl/fl, Camk2a-Cre; G9afl/fl and age (10-14 week old) and sex matched littermate controls were used for total RNA purification. Four biological replicates were performed for each experiment. Polyribosome associated mRNAs from five, age (10-14 week old) and sex matched Drd1-Cre; Drd1-bacTRAP; G9afl/fl, or Drd2-Cre; Drd2-bacTRAP; G9afl/fl and Drd1-bacTRAP; G9afl/fl or Drd2-bacTRAP; G9afl/fl control mice were used. Three biological replicates were performed for each experiment.
2009-12-10 | E-GEOD-19402 | biostudies-arrayexpress
