GeneSet Information

Tier IV GS409781 • Differentially expressed genes (TRAP-seq) in mouse MOR neurons from paraventricular nucleus of the thalamus (PVT) MOR's morphine vs control_qvalue

DESCRIPTION:

Mice exposed to morphine drank about 5mL per animal per day (Fig. 1A). Male and female mice on a C57Bl/6J background were used in all studies. Experiments to manipulate mu-opioid receptor-expressing neurons used MOR-Cre mice developed in our lab. These MOR-Cre mice were then crossed with RosaLSLSun1-sfGFP [29] to generate a reporter line for visualization of MORs or Rosa26LSL-EGFP-L10a [30] for cell-type specific RNA sequencing. Mice were 8–12 weeks at the start of each experiment. Mice were sacrificed between 1200 and 1400h and, for each mouse, a gross dissection targeted at the PVT was used to generate tissue for the translating ribosome affinity purification (TRAP). We used both control mice and mice exposed to chronic morphine for TRAP. Due to the small amount of brain tissue, 2 PVT dissections were pooled together to create each biological sample—males were only pooled with males and females were only pooled with females, for a total of four biological replicates for each of the morphine and control groups. RNA sequencing of the MOR+expressing neurons in the PVT that were affinity purified by Translating Ribosome Affinity Purification (TRAP) and subsequent DE analysis identified 311 upregulated and 211 downregulated genes in the morphine group as compared to the control group (multiple-testing-adjusted P value <0.05).

LABEL:

DEG mouse PVT MOR's morphine vs control_qvalue

SCORE TYPE:

Q-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

520

DATE ADDED:

2024-12-26

DATE UPDATED:

2024-12-26

SPECIES:

AUTHORS:

Darrell Eacret, Elisabetta Manduchi, Julia Noreck, Emma Tyner, Polina Fenik, Amelia D Dunn, Jonathan Schug, Sigrid C Veasey, Julie A Blendy

TITLE:

Mu-opioid receptor-expressing neurons in the paraventricular thalamus modulate chronic morphine-induced wake alterations.

JOURNAL:

Translational psychiatry Mar 2023, Vol 13, pp. 78

ABSTRACT:

Disrupted sleep is a symptom of many psychiatric disorders, including substance use disorders. Most drugs of abuse, including opioids, disrupt sleep. However, the extent and consequence of opioid-induced sleep disturbance, especially during chronic drug exposure, is understudied. We have previously shown that sleep disturbance alters voluntary morphine intake. Here, we examine the effects of acute and chronic morphine exposure on sleep. Using an oral self-administration paradigm, we show that morphine disrupts sleep, most significantly during the dark cycle in chronic morphine, with a concomitant sustained increase in neural activity in the Paraventricular Nucleus of the Thalamus (PVT). Morphine binds primarily to Mu Opioid Receptors (MORs), which are highly expressed in the PVT. Translating Ribosome Affinity Purification (TRAP)-Sequencing of PVT neurons that express MORs showed significant enrichment of the circadian entrainment pathway. To determine whether MOR + cells in the PVT mediate morphine-induced sleep/wake properties, we inhibited these neurons during the dark cycle while mice were self-administering morphine. This inhibition decreased morphine-induced wakefulness but not general wakefulness, indicating that MORs in the PVT contribute to opioid-specific wake alterations. Overall, our results suggest an important role for PVT neurons that express MORs in mediating morphine-induced sleep disturbance. PUBMED: 36869037
Find other GeneSets from this publication

Annotation Information

No sequence read archive data associated with this GeneSet.


Wakefulness (D014851)
Animals (D000818)
Negotiating (D017008)
Substance-Related Disorders (D019966)
Paraventricular Hypothalamic Nucleus (D010286)
Biological Products (D001688)
Mental Disorders (D001523)
Dissection (D004210)
Thalamus (D013788)
Ribosomes (D012270)
Neurons (D009474)
Overall (D016424)
Receptors, Opioid, mu (D017450)
Pharmaceutical Preparations (D004364)
Tissues (D014024)
Sequence Analysis, RNA (D017423)
Organization and Administration (D009934)
Control Groups (D035061)
Morphine (D009020)
Receptors, Opioid (D011957)
Translating (D014175)
Analgesics, Opioid (D000701)
Data acquisition and deposition (EDAM_topic:3077)
Cell biology resources (EDAM_topic:2229)
Pathway or network (EDAM_data:2600)
maleate(2-) (CHEBI:30780)
ribonucleic acid (CHEBI:33697)
atomic nucleus (CHEBI:33252)
morphine(1+) (CHEBI:58097)
Sleep disturbance (HP:0002360)
Behavioral abnormality (HP:0000708)
RNA-seq evidence (ECO:0000295)
dissection (EFO:0003856)
experimental process (EFO:0002694)
paraventricular nucleus of hypothalamus (UBERON:0001930)
rostral octaval nerve motor nucleus (UBERON:2002175)
dorsal plus ventral thalamus (UBERON:0001897)
male organism (UBERON:0003101)
female organism (UBERON:0003100)
neural nucleus (UBERON:0000125)
paraventricular nucleus of thalamus (UBERON:0001920)
adult cerebral ganglion (UBERON:6110636)

Gene List • 520 Genes

Genes in threshold: 520

Uploaded As Gene Symbol Homology Score Priority LinkOuts Emphasis