Mus musculus
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PROVIDER: PRJNA121769 | ENA |
REPOSITORIES: ENA
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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
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.
2009-12-10 | GSE19402 | GEO
Project description:A more complete understanding of the molecular mechanisms by which substance use is encoded in the brain could illuminate novel strategies to treat substance use disorders, including cocaine use disorder (CUD). We have previously discovered that Zfp189, which encodes a Krüppel-associated box zinc finger protein (KZFP) transcription factor (TF), differentially accumulates in nucleus accumbens (NAc) Drd1+ and Drd2+ medium spiny neurons (MSNs) over the course of cocaine exposure and is causal in producing MSN functional and behavioral changes to cocaine. Here, we aimed to illuminate the brain cell-type specific molecular mechanisms through which this KZFP TF produces chronic cocaine -related brain changes, with emphasis on investigating transposable elements (TEs), since KZFPs like ZFP189 are known regulators of TEs. We discovered that expression of NAc TE transcripts was dramatically increased by cocaine experience, the most sensitive NAc cell-type was MSNs, and TEs in Drd1+ MSNs were considerably more dynamic over the course of cocaine exposure than TEs in Drd2+ MSNs. We demonstrated that synthetic ZFP189VPR is capable of dysregulating NAc TEs. In our snRNAseq data we observed that, relative to ZFP189WT, NAc manipulated with ZFP189VPR impeded cocaine-induced gene expression in NAc cell-types, including both Drd1+ and Drd2+ MSNs. Within either MSN subtype, the consequence of normal ZFP189 function was to enhance immune-related gene expression, and ZFP189VPR impeded these gene expression profiles. We discovered that behavioral and cell morphological adaptations to cocaine are produced by dysregulating TEs with ZFP189VPR in Drd1+ MSNs or stabilizing TEs with ZFP189WT in Drd2+ MSNs, revealing a persistent opponent process balanced across MSN subtypes and weighted by TE stability and consequent gene expression within MSN subtype.
2025-08-27 | GSE296548 | GEO
Project description:A more complete understanding of the molecular mechanisms by which substance use is encoded in the brain could illuminate novel strategies to treat substance use disorders, including cocaine use disorder (CUD). We have previously discovered that Zfp189, which encodes a Krüppel-associated box zinc finger protein (KZFP) transcription factor (TF), differentially accumulates in nucleus accumbens (NAc) Drd1+ and Drd2+ medium spiny neurons (MSNs) over the course of cocaine exposure and is causal in producing MSN functional and behavioral changes to cocaine. Here, we aimed to illuminate the brain cell-type specific molecular mechanisms through which this KZFP TF produces chronic cocaine -related brain changes, with emphasis on investigating transposable elements (TEs), since KZFPs like ZFP189 are known regulators of TEs. We discovered that expression of NAc TE transcripts was dramatically increased by cocaine experience, the most sensitive NAc cell-type was MSNs, and TEs in Drd1+ MSNs were considerably more dynamic over the course of cocaine exposure than TEs in Drd2+ MSNs. We demonstrated that synthetic ZFP189VPR is capable of dysregulating NAc TEs. In our snRNAseq data we observed that, relative to ZFP189WT, NAc manipulated with ZFP189VPR impeded cocaine-induced gene expression in NAc cell-types, including both Drd1+ and Drd2+ MSNs. Within either MSN subtype, the consequence of normal ZFP189 function was to enhance immune-related gene expression, and ZFP189VPR impeded these gene expression profiles. We discovered that behavioral and cell morphological adaptations to cocaine are produced by dysregulating TEs with ZFP189VPR in Drd1+ MSNs or stabilizing TEs with ZFP189WT in Drd2+ MSNs, revealing a persistent opponent process balanced across MSN subtypes and weighted by TE stability and consequent gene expression within MSN subtype.
2025-08-27 | GSE296397 | GEO
Project description:Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological, and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we find that G9a repression by cocaine occurs in both Drd1 (striatonigral)- and Drd2 (striatopallidal)-expressing medium spiny neurons (MSNs). Conditional knockout and overexpression of G9a within these distinct cell types, however, reveals divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicate that such developmental deletion of G9a selectively in Drd2 neurons results in the unsilencing of transcriptional programs normally specific to striatonigral neurons, and the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral ‘switching’ phenotype in mice indicates a novel role for G9a in contributing to neuronal subtype identity, and suggests a critical function for cell-type specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli. Polyribosome associated mRNAs from 2-5 month old, age and sex matched Drd1-Cre; Drd1-TRAP; G9afl/fl and Drd1-TRAP; G9afl/fl, Drd2-Cre; Drd2-TRAP; G9afl/fl and Drd2-TRAP; G9afl/fl mice (n = 2-4 mice/genotype/drug treatment, 2 hours after the last of eight repeated cocaine injections of 20 mg/kg/day) were obtained as previously described. EGFP labeled ribosomes and associated mRNAs were immunoprecipitated using a mix of two monoclonal anti-GFP antibodies (50 μg of clones #19C8 and #19F7 for each IP, available at Sloan-Kettering Monoclonal Antibody Facility). Purified mRNA was amplified and processed for microarray and qPCR analysis using the Affymetrix two-cycle cDNA Synthesis kit (Affymetrix) as previously described. Affymetrix Mouse Genome 430 2.0 arrays were used in all experiments. Information regarding the array design and features can be found at www.affymetrix.com. Mouse Genome 430 2.0 arrays were scanned using the GeneChip Scanner 3000 (Affymetrix) and globally scaled to 150 using the Affymetrix GeneChip Operating Software (GCOS v1.4).
2014-02-05 | E-GEOD-54656 | biostudies-arrayexpress
Project description:We report single-nucleus transcriptomes from brain regions in 5 species: mice: Frontal Cortex, V1, Hippocampus, Striatum; common marmoset: 7 neocortical regions, Hippocampus, Striatum (Nucleus Accumbens, Caudate, Putamen); rhesus macaque: Prefrontal Cortex, V1; human: Prefrontal Cortex, V1, Striatum (Caudate); ferret: Prefrontal Cortex, V1, Striatum
2020-06-04 | GSE151761 | GEO
Project description:Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological, and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we find that G9a repression by cocaine occurs in both Drd1 (striatonigral)- and Drd2 (striatopallidal)-expressing medium spiny neurons (MSNs). Conditional knockout and overexpression of G9a within these distinct cell types, however, reveals divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicate that such developmental deletion of G9a selectively in Drd2 neurons results in the unsilencing of transcriptional programs normally specific to striatonigral neurons, and the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral ‘switching’ phenotype in mice indicates a novel role for G9a in contributing to neuronal subtype identity, and suggests a critical function for cell-type specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli.
2014-02-05 | GSE54656 | GEO
Project description:The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9 positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSNs identity and repressing D1-MSNs identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2 like-MSNs survived normally in adulthood. Taken together, our finding supported that Sp9 was sufficient to promote D2-MSNs identity and repress D1-MSNs identity, and Sp9 was a negative regulator of D1-MSNs fate. The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9 positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSNs identity and repressing D1-MSNs identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2 like-MSNs survived normally in adulthood. Taken together, our finding supported that Sp9 was sufficient to promote D2-MSNs identity and repress D1-MSNs identity, and Sp9 was a negative regulator of D1-MSNs fate.
2022-07-06 | GSE202550 | GEO
Project description:N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline (30-80 Hz) frequency oscillations. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. MK-801 increases the synchrony of baseline oscillations, causing very early changes in gene expressions in rat brain after acute MK-801 treatment, a first report. The overall goal of the present study was to identify gene expression patterns along rat chromosomes in different brain regions after a single injection of MK-801, which exerts a longer acute effect than ketamine on ongoing brain activities. Two approaches were taken, first electrophysiological and send molecular analysis, where the brain of MK-801-treated rats was subjected to a genome-wide transcriptome mapping analysis (~4400 genes) in the cerebral cortex, midbrain, hippocampus, ventral striatum, amygdala, and hypothalamus regions.
2014-11-26 | E-GEOD-63639 | biostudies-arrayexpress
Project description:Interleukin (IL)-18 is recognized as a multifunctional mediator in inflammation and immune responses. In addition, the production of IL-18 is stimulated by physiological and/or psychological stress implicated in several behavioral disorders. However, it still remains unclear about the role of IL-18 on the central nervous system. In this study, we analyzed gene expression of 6 brain regions; the olfactory bulb, prefrontal cortex, striatum, amygdala, hypothalamus, and hippocampus. Microarray analysis indicated the regional differences of expression in IL-18-/- mice. In particular, the most profound change was observed in the amygdala, in which 1,237 genes were differentially expressed. We purchased IL-18-/- mice and C57BL/6 mice from Charles River Japan . To produce F1 generation mice, three male IL-18-/- mice were mated with six female C57BL/6J mice. We mated F1 mice and created their F2 littermates. Six week-old F2 mice littermates were weaned. At 12 weeks, mice were sacrificed at 14:00 under general anesthesia with diethyl ether. After the systemic perfusion with cold phosphate-buffered saline through the heart using a syringe attached to a 21-G needle, the whole mouse brains were removed. Coronal brain sections (1 mm thick) were prepared on ice using a brain slicer . The olfactory bulb was sliced between 3.5 and 4.5 anterior to bregma. The prefrontal cortex was sliced between 2.5 and 3.5 mm anterior to bregma. The striatum was sliced between -0.5 and 0.5 mm posterior to bregma. The hypothalamus, the amygdala, and the hippocampus were sliced between 1.5 and 2.5 mm posterior to bregma. Total RNA was immediately prepared from these samples using TRIzol and purified by RNeasy kit.
2010-12-01 | E-GEOD-19522 | biostudies-arrayexpress