Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment
Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these etha...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-09-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fped.2014.00103/full |
| _version_ | 1818481024294715392 |
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| author | Cherry eIgnacio Sandra M Mooney Frank A Middleton |
| author_facet | Cherry eIgnacio Sandra M Mooney Frank A Middleton |
| author_sort | Cherry eIgnacio |
| collection | DOAJ |
| description | Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of Social Enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or Social Enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by Social Enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for Social Enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression. |
| first_indexed | 2024-12-10T11:29:57Z |
| format | Article |
| id | doaj.art-8157b67fcc91479b8acdb320b6725a87 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-10T11:29:57Z |
| publishDate | 2014-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-8157b67fcc91479b8acdb320b6725a872022-12-22T01:50:38ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602014-09-01210.3389/fped.2014.00103109620Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichmentCherry eIgnacio0Sandra M Mooney1Frank A Middleton2SUNY Upstate Medical UniversityUniversity of Maryland, BaltimoreSUNY Upstate Medical UniversityFetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of Social Enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or Social Enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by Social Enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for Social Enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.http://journal.frontiersin.org/Journal/10.3389/fped.2014.00103/fullAmygdalaFetal Alcohol SyndromeGene ExpressionSocial Behavioradolescenceventral striatum |
| spellingShingle | Cherry eIgnacio Sandra M Mooney Frank A Middleton Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment Frontiers in Pediatrics Amygdala Fetal Alcohol Syndrome Gene Expression Social Behavior adolescence ventral striatum |
| title | Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment |
| title_full | Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment |
| title_fullStr | Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment |
| title_full_unstemmed | Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment |
| title_short | Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment |
| title_sort | effects of acute prenatal exposure to ethanol on microrna expression are ameliorated by social enrichment |
| topic | Amygdala Fetal Alcohol Syndrome Gene Expression Social Behavior adolescence ventral striatum |
| url | http://journal.frontiersin.org/Journal/10.3389/fped.2014.00103/full |
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