Transcriptomics,Genomics

Dataset Information

33

Neonatal morphine exposure alters mRNA and microRNA (miR) expression in mouse hippocampus


ABSTRACT: Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR gene expression. C57BL/6 male mice were treated from postnatal day (P) 5 to P9 with morphine at 2 or 5 mg/kg ip bid (MS5) and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min) followed by 2h maternal separation. Control mice were untreated and dam-reared. mRNA and microRNA expression profiling was performed on hippocampal tissues at P9. Overall, MS2 and MS5 morphine treatment altered expression of a total of 150 mRNAs (>1.5 fold change, P<0.05; 36 up, 114 down), and MS5 affected 63 mRNAs. The most upregulated mRNAs were fidgetin, arginine vasopressin, and resistin-like alpha, and the most down-regulated were defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel 6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment affected pathways related to cell cycle, membrane function, signaling, metabolism, cell death, transcriptional regulation, and immune response. MS5 decreased expression of miR-204-5p, miR-455-3p, miR-448-3p, and miR-574-3p.Nine morphine-responsive mRNAs that are involved in neurodevelopment, neurotransmission, and inflammation are predicted targets of the aforementioned differentially expressed microRNAs These data establish that morphine produces dose-dependent changes in both hippocampal mRNA and miR gene expression in stressed neonatal mice. If permanent, morphine–mediated neuroepigenetic effects may affect long-term hippocampal function, and this provides a mechanism for the neonatal morphine-related impairment of adult learning. Overall design: Beginning on P5, male mice were assigned to one of 3 treatment conditions: untreated control (Con), morphine 2 mg/kg + stress (MS2), and morphine 5 mg/kg + stress (MS5). Untreated control animals were housed normally and exposed to minimal handling. Treated pups were exposed to stress, apnea, and morphine. To produce stress, mice were separated from the dam and isolated in cups within a veterinary warmer at 32°C (08:00 h to16:00 h). To simulate apnea, mice were exposed to 100% N2 for 1 min then 100% O2 for 5 min, twice daily (08:00 and 15:30 h). Just prior to each apnea exposure, mice received 10 µL s.c. injections of morphine. After treatments, mice were then returned to the home cage with the untreated control littermates and could nurse overnight ad lib.

INSTRUMENT(S): Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)

SUBMITTER: James William MacDonald  

PROVIDER: GSE62346 | GEO | 2015-10-05

SECONDARY ACCESSION(S): PRJNA263916

REPOSITORIES: GEO

altmetric image

Publications

Dose-dependent effects of morphine exposure on mRNA and microRNA (miR) expression in hippocampus of stressed neonatal mice.

McAdams Ryan M RM   McPherson Ronald J RJ   Beyer Richard P RP   Bammler Theo K TK   Farin Frederico M FM   Juul Sandra E SE  

PloS one 20150406 4


Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were treated from postnatal day (P) 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip twice daily and then exp  ...[more]

Similar Datasets

2013-08-30 | E-GEOD-50382 | ArrayExpress
| PRJNA217692 | ENA
2016-01-07 | E-GEOD-74145 | ArrayExpress
2013-08-01 | E-GEOD-42506 | ArrayExpress
2010-05-19 | E-GEOD-14268 | ArrayExpress
2009-05-04 | GSE14268 | GEO
| GSE83636 | GEO
| EGAD00001000775 | EGA
| PRJNA263916 | ENA
2013-03-05 | E-GEOD-44906 | ArrayExpress