Epigenomic profiling of H3K27ac in mouse brain regions under morphine and LPS exposure
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE332794 | GEO | 2026/06/17
REPOSITORIES: GEO
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Project description:We profiled genome-wide gene expression across four brain regions (hippocampus, prefrontal cortex, striatum, and hypothalamus) in male and female C57BL/6NTac mice using a perinatal morphine exposure model of Neonatal Opioid Withdrawal Syndrome (NOWS). Mice received morphine or saline perinatally, then were challenged with LPS or saline in adulthood, yielding four groups (SAL-SAL, SAL-LPS, MOR-SAL, MOR-LPS). NeuN+ neuronal nuclei (~5,000 per sample) were isolated by FACS from PFC, hippocampus, hypothalamus, and striatum and profiled by RNA-seq (Illumina NovaSeq X Plus, paired-end 150 bp). RNA-seq identified differentially expressed genes enriched in immune and metabolic pathways, with the hypothalamus displaying the most pronounced transcriptional response to perinatal morphine exposure.
2026-06-17 | GSE332798 | GEO
Project description:To study the relationship between microRNAs and μ-opioid receptor (MOR) signaling, we examined microRNA expression after chronic morphine or fentanyl treatment in rat primary hippocampal neurons and in mouse hippocampus. Mouse cerebellum region was also tested as a negative control to eliminate microRNA expression changes unrelated to MOR signaling, as the cerebellum is essentially devoid of MOR. We identified a number of microRNAs that altered their expression upon treatment with both morphine and fentanyl in the rat and mouse systems. There were, however, some microRNAs that changed in response to morphine, or fentanyl, but not both. Keywords: Expression profiling
2009-05-04 | GSE14268 | GEO
Project description:Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Current treatments involve non-pharmacological and pharmacological interventions, however, there is no one standardized approach, in part because of variability in NOWS severity. To effectively model NOWS traits in mice, we used a third trimester-approximate opioid exposure paradigm, where neonatal inbred FVB/NJ and outbred Carworth Farms White (CFW) pups were injected twice-daily with morphine (10-15 mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day (P) one to P14. We observed reduced body weight gain, hypothermia, thermal hyperalgesia, and increased ultrasonic vocalizations (USVs). Neonatal USVs are emitted exclusively in isolation to communicate distress and thus serve as a model behavior for affective states. On P14, we observed altered USV syllable profiles during spontaneous morphine withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males) and in CFW mice of both sexes. Brainstem transcriptomics revealed an upregulation of the kappa opioid receptor (Oprk1), whose activation has previously been shown to contribute to withdrawal-induced dysphoria. Treatment with the kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USV emission in FVB/NJ females, but not FVB/NJ males during spontaneous morphine withdrawal. Furthermore, treatment with the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USV emission on P10 (both sexes) and on P14 (females only) in FVB/NJ mice. Together, these results indicate a female-specific recruitment of the dynorphin/KOR system in neonatal opioid withdrawal symptom severity.
2024-07-09 | GSE271337 | GEO
Project description:Ligand-dependent differences in the regulation and internalization of the mu-opioid receptor (MOR) have been linked to the degree of severity of the side effects that limit the use of opiates in the treatment of pain. For example, activation of the MOR by morphine and DAMGO ([D-Ala2,N-MePhe4,Gly-ol]-enkephalin) causes distinct patterns of spatiotemporal signaling which are dependent on the distribution pattern of the receptor at the plasma membrane after activation. Morphine stimulation of MOR activates a Gβγ-protein kinase C (PKC)α-phosphorylation pathway that limits the distribution of the MOR and is associated with a sustained increase in cytosolic extracellular signal regulated kinase (ERK). In contrast, DAMGO causes a redistribution of the MOR at the plasma membrane (prior to receptor internalization), that facilitates transient activation of cytosolic and nuclear ERK. Here, we use proximity biotinylation proteomics to dissect the different protein-interaction networks that underlie the spatiotemporal signaling of morphine and DAMGO. We found that DAMGO, but not morphine, activates Rac1 (Ras‐related C3 botulinum toxin substrate 1). Rac1 activation is dependent on the scaffolding proteins IQ motif-containing GTPase-activating protein-1 (IQGAP1) and Crk-like protein (CRKL), and CRKL is required for the transient increase in nuclear ERK. In contrast, morphine increased the proximity of the MOR to desmosomes, specialized and highly-ordered membrane domains. Knockdown of desmosomal proteins junction plakoglobin (JUP) or desmocolin-1 (DSC1) switched the morphine spatiotemporal signaling profile to mimic that of DAMGO, revealing a transient increase in nuclear ERK. Identifying the MOR-interaction networks that control differential spatiotemporal signaling represents an important step towards understanding how signal compartmentalization contributes to the development of tolerance and dependence.
2019-09-26 | PXD013328 | Pride
Project description:To study the relationship between microRNAs and μ-opioid receptor (MOR) signaling, we examined microRNA expression after chronic morphine or fentanyl treatment in rat primary hippocampal neurons and in mouse hippocampus. Mouse cerebellum region was also tested as a negative control to eliminate microRNA expression changes unrelated to MOR signaling, as the cerebellum is essentially devoid of MOR. We identified a number of microRNAs that altered their expression upon treatment with both morphine and fentanyl in the rat and mouse systems. There were, however, some microRNAs that changed in response to morphine, or fentanyl, but not both. Keywords: Expression profiling There are up to three biological replicates (indicated by 1, 2, and 3) of primary hippocampal neurons from new born rats and the cerebellum and hippocampus regions from adult mice treated for three days (control, morphine, and fentanyl). The biological replicates were from experiments performed on different dates. Each biological replicate contained cells or tissues collected from multiple animals so that enough RNA could be extracted for RNA analysis. RNA was labelled with a green dye, mixed with a reference DNA sample labelled with a red dye. The reference DNA contained a number of synthetic DNA oligos with mature microRNA sequences that served to verify microarray hybridization. RNA signals were in ch1, DNA signals ch2.
2010-05-19 | E-GEOD-14268 | biostudies-arrayexpress
Project description:Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS is revealed upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and erratic feeding. The main pharmacological treatment strategy for alleviating symptoms is opioid maintenance therapy. The neural mechanisms mediating NOWS and the long-term neurobehavioral effects are poorly understood. We used a third trimester-approximate model in which neonatal outbred pups (Cartworth Farms White; CFW) were administered once-daily morphine (15 mg/kg, s.c.) from postnatal day (P) day 1 through P14 and were then assessed for behavioral and transcriptomic adaptations within the nucleus accumbens (NAc) on P15. We also investigated the long-term effects of perinatal morphine exposure on adult learning and reward sensitivity. We observed significant weight deficits, spontaneous thermal hyperalgesia, and altered ultrasonic vocalization (USV) profiles following repeated morphine and during spontaneous withdrawal. Transcriptome analysis of NAc from opioid-withdrawn P15 neonates via bulk mRNA sequencing identified an enrichment profile consistent with downregulation of myelin-associated transcripts. Despite the neonatal behavioral and molecular effects, there were no significant long-term effects of perinatal morphine exposure on adult spatial memory function in the Barnes Maze, emotional learning in fear conditioning, or in baseline or methamphetamine-potentiated reward sensitivity as measured via intracranial self-stimulation. Thus, the once daily third trimester-approximate exposure regimen, while inducing NOWS model traits and significant transcriptomic effects in neonates, had no significant long-term effects on adult behaviors.
2023-08-03 | GSE239919 | GEO
Project description:we derived, validated, and applied a novel MOR-specific Cre mouse line, inserting a T2A cleavable peptide sequence and the Cre coding sequence into the MOR 3’UTR. Importantly, this line shows specificity and fidelity of MOR expression throughout the brain and with respect to function, there were no differences in behavioral responses to morphine when compared to wild type mice, nor are there any alterations in Oprm1 gene expression or receptor density. To assess Cre recombinase activity, MOR-Cre mice were crossed with the floxed GFP-reporters, RosaLSLSun1-sfGFP or RosaLSL-GFP-L10a. The latter allowed for cell type specific RNA sequencing via TRAP (Translating Ribosome Affinity Purification) of striatal MOR+ neurons following opioid withdrawal.
2023-01-01 | GSE218564 | GEO
Project description:Single nuclear RNA-sequencing from tissue dissected from the ventral medial preoptic area (VMPO) of the hypothalamus in saline and LPS injected mice
2022-03-02 | GSE197547 | GEO
Project description:We developed a mouse model of NOWS that includes gestational and post-natal morphine exposure that encompasses the developmental equivalent of all three human trimesters of gestation. This exposure paradigm causes delayed developmental milestones and acute withdrawal phenotypes reminiscent of those observed in infants.
2023-12-15 | GSE225468 | GEO
Project description:Addictive drugs including opioids activate signal transduction pathways that regulate gene expression in the brain. However, changes in CNS gene expression following morphine exposure are poorly understood. We studied the effect of short- and long-term morphine treatment on gene expression in the hypothalamus and pituitary using genome-wide DNA microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses. In the hypothalamus, we found that short-term morphine administration up-regulated (at least 2-fold) 39 genes and down-regulated six genes. Long-term morphine administration up-regulated 35 genes and down-regulated 51 hypothalamic genes. In the pituitary, we found that short-term morphine administration up-regulated (at least 2-fold) 110 genes and down-regulated 29 genes. Long-term morphine administration up-regulated 85 genes and down-regulated 37 pituitary genes. Strikingly, microarray analysis uncovered several genes involved in food intake (neuropeptide Y, agouti-related protein, and cocaine and amphetamine-regulated transcript) whose expression was strongly altered by morphine exposure in either the hypothalamus or pituitary. Subsequent RT-PCR analysis confirmed similar gene regulation of noteworthy genes in these regions. Finally, we found functional correlation between morphine-induced alterations in food intake and regulations of genes involved in this process. Changes in genes related to food intake may uncover new pathways related to some of the physiological effects of opioids. Keywords: Comparative treatment versus placebo 8 samples analyzed: 4 from hypothalamus (2 biological replicates and 2 dye swaps) and 4 from pituitary (2 biological replicates and 2 dye swaps) 8 samples analyzed: 4 from hypothalamus short term treatment (2 biological replicates and 2 dye swaps) and 4 hypothalamus long term treatment (2 biological replicates and 2 dye swaps)
2008-09-30 | E-GEOD-9525 | biostudies-arrayexpress