GeneSet Information

Tier IV GS409819 • Perinatal fentanyl exposed vs control differentially expressed genes in male mouse ventral tegmental area (VTA)_pvalue

DESCRIPTION:

We identified individual genes with significant gene expression changes following perinatal fentanyl exposure. Pregnant C57BL/6 dams received 10μg/ml fentanyl in their drinking water from embryonic day 0 (E0) through birth until weaning at postnatal day 21 (P21). Liquid consumption by dams all through gestation to weaning was comparable between water and fentanyl in water group. Post-weaning, at P35, we performed an unbiased transcriptomic analysis in perinatal fentanyl exposed mice using high-throughput RNAseq of bulk-tissue punches from VTA, NAc, PrL, S1 and VBT from four juvenile (P35) mice per sex/treatment. For RNA sequencing, only samples with RNA integrity numbers >8 were used. Samples were sequenced on an Illumina HiSeq 4000 with a 75bp paired-end read. 64–100 million reads were obtained for each sample. Reads were aligned to the mouse genome (Mus musculus. GRCm38) using TopHat2 (version 2.0.8; maximum number of mismatches=2; segment length=30; maximum multi-hits per read=25; maximum intron length=50,000). A False Discovery Rate (FDR)<0.05 was used to define differentially expressed genes.

LABEL:

Perinatal fentanyl exposed DEG in male mouse VTA_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

2910

DATE ADDED:

2024-12-31

DATE UPDATED:

2024-12-31

SPECIES:

AUTHORS:

Jimmy Olusakin, Gautam Kumar, Mahashweta Basu, Cali A Calarco, Megan E Fox, Jason B Alipio, Catherine Haga, Makeda D Turner, Asaf Keller, Seth A Ament, Mary Kay Lobo

TITLE:

Transcriptomic profiling of reward and sensory brain areas in perinatal fentanyl exposed juvenile mice.

JOURNAL:

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Nov 2023, Vol 48, pp. 1724-1734

ABSTRACT:

Use of the synthetic opioid fentanyl increased ~300% in the last decade, including among women of reproductive ages. Adverse neonatal outcomes and long-term behavioral disruptions are associated with perinatal opioid exposure. Our previous work demonstrated that perinatal fentanyl exposed mice displayed enhanced negative affect and somatosensory circuit and behavioral disruptions during adolescence. However, little is known about molecular adaptations across brain regions that underlie these outcomes. We performed RNA sequencing across three reward and two sensory brain areas to study transcriptional programs in perinatal fentanyl exposed juvenile mice. Pregnant dams received 10 μg/ml fentanyl in the drinking water from embryonic day 0 (E0) through gestational periods until weaning at postnatal day 21 (P21). RNA was extracted from nucleus accumbens (NAc), prelimbic cortex (PrL), ventral tegmental area (VTA), somatosensory cortex (S1) and ventrobasal thalamus (VBT) from perinatal fentanyl exposed mice of both sexes at P35. RNA sequencing was performed, followed by analysis of differentially expressed genes (DEGs) and gene co-expression networks. Transcriptome analysis revealed DEGs and gene modules significantly associated with exposure to perinatal fentanyl in a sex-wise manner. The VTA had the most DEGs, while robust gene enrichment occurred in NAc. Genes enriched in mitochondrial respiration were pronounced in NAc and VTA of perinatal fentanyl exposed males, extracellular matrix (ECM) and neuronal migration enrichment were pronounced in NAc and VTA of perinatal fentanyl exposed males, while genes associated with vesicular cycling and synaptic signaling were markedly altered in NAc of perinatal fentanyl exposed female mice. In sensory areas from perinatal fentanyl exposed females, we found alterations in mitochondrial respiration, synaptic and ciliary organization processes. Our findings demonstrate distinct transcriptomes across reward and sensory brain regions, with some showing discordance between sexes. These transcriptome adaptations may underlie structural, functional, and behavioral changes observed in perinatal fentanyl exposed mice. PUBMED: 37400565
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Annotation Information

No sequence read archive data associated with this GeneSet.


Brain (D001921)
Drinking (D004326)
RNA (D012313)
Weaning (D014886)
Economics (D004467)
Fentanyl (D005283)
Genome (D016678)
Mice (D051379)
Gene Regulatory Networks (D053263)
Gene Expression Profiling (D020869)
Thalamus (D013788)
Gene Expression (D015870)
Adolescent (D000293)
Water (D014867)
Therapeutics (D013812)
Respiration (D012119)
Work (D014937)
Extracellular Matrix (D005109)
Sex (D012723)
Tissues (D014024)
Nucleus Accumbens (D009714)
Ventral Tegmental Area (D017557)
Somatosensory Cortex (D013003)
Genes (D005796)
Affect (D000339)
Sequence Analysis, RNA (D017423)
Organizations (D009938)
Women (D014930)
Reward (D012201)
Programs (D019542)
Introns (D007438)
Parturition (D036801)
Pregnancy (D011247)
Analgesics, Opioid (D000701)
accumbens nucleus (MA:0000892)
thalamus (MA:0000179)
brain (MA:0000168)
interleukin-35 complex (GO:0070745)
female pregnancy (GO:0007565)
neuron migration (GO:0001764)
nascent polypeptide-associated complex (GO:0005854)
extracellular region (GO:0005576)
nucleus (GO:0005634)
extracellular matrix (GO:0031012)
respiratory gaseous exchange (GO:0007585)
gene expression (GO:0010467)
signaling (GO:0023052)
cellular respiration (GO:0045333)
interleukin-12 complex (GO:0043514)
RNA (EDAM_topic:0099)
Analysis (EDAM_operation:2945)
Genetics (EDAM_topic:3053)
Sequencing (EDAM_topic:3168)
Transcriptomics (EDAM_topic:0203)
Matrix (EDAM_data:2082)
Pathways, networks and models (EDAM_topic:0602)
Keyword (EDAM_data:0968)
RNA-Seq (EDAM_topic:3170)
rna (EDAM_format:1213)
N-acetyl-L-cysteine (CHEBI:28939)
fentanyl (CHEBI:119915)
group (CHEBI:24433)
Prolactin (CHEBI:81580)
water (CHEBI:15377)
NAC (CHEBI:7421)
advanced glycation end-product (CHEBI:84123)
ribonucleic acid (CHEBI:33697)
atomic nucleus (CHEBI:33252)
Behavioral abnormality (HP:0000708)
Mitochondrial inheritance (HP:0001427)
RNA-seq evidence (ECO:0000295)
exposure (EFO:0000487)
individual (EFO:0000542)
treatment (EFO:0000727)
C57BL (EFO:0005181)
ventral (EFO:0001662)
postnatal (EFO:0002948)
obsolete_accumbens nucleus (EFO:0000906)
area (EFO:0001696)
obsolete_adult segment (EFO:0000961)
obsolete_ventral tegmental area (EFO:0001935)
neonate (EFO:0001372)
rectal adenocarcinoma (EFO:0005631)
pregnancy (EFO:0002950)
transcriptome (EFO:0004421)
genome (EFO:0004420)
parturition trait (VT:0002907)
cortex (UBERON:0001851)
start of neonate stage (UBERON:0035946)
muscle structure (UBERON:0005090)
dorsal plus ventral thalamus (UBERON:0001897)
brain (UBERON:0000955)
postcentral gyrus (UBERON:0002581)
somatosensory cortex (UBERON:0008930)
tissue (UBERON:0000479)
female organism (UBERON:0003100)
neural nucleus (UBERON:0000125)
ventral tegmental area (UBERON:0002691)
sexually immature organism (UBERON:0007021)
postsubiculum (UBERON:0035971)
nucleus accumbens (UBERON:0001882)
anatomical projection (UBERON:0004529)
adult cerebral ganglion (UBERON:6110636)
abomasum (UBERON:0007358)
organismal segment (UBERON:0000914)
matrix compartment (UBERON:0027368)
synaptic signaling (GO:0099536)
tissue (MA:0003002)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

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