Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus

Proopiomelanocortin (POMC) is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC g...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2014-11, Vol.9 (11), p.e113228-e113228
Hauptverfasser: Gangisetty, Omkaram, Bekdash, Rola, Maglakelidze, George, Sarkar, Dipak K
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e113228
container_issue 11
container_start_page e113228
container_title PloS one
container_volume 9
creator Gangisetty, Omkaram
Bekdash, Rola
Maglakelidze, George
Sarkar, Dipak K
description Proopiomelanocortin (POMC) is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA) axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2) in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA) axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC) of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH) gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH) and corticosterone hormone responses to lipopolysaccharide (LPS) challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.
doi_str_mv 10.1371/journal.pone.0113228
format Article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1980724928</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_948cc3d0fd824219931ec71c9dea9e56</doaj_id><sourcerecordid>1980724928</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-2ba9e9b050da395598c65fe0ea5a1d0b7ad9b4746e0fc82cc6bfcbc15477e4b13</originalsourceid><addsrcrecordid>eNptUk1v1DAUjBCIlsI_QBCJC5cs_ozjC1JVUahUBAc4W47zsuuV1w62U7V_iN-Jw26rLUI-2HqemffGnqp6jdEKU4E_bMMcvXarKXhYIYwpId2T6hRLSpqWIPr06HxSvUhpixCnXds-r04IZ0iWdVr9voSsXa2dCZvgaridQpojlEKGmOophjDZsAOnfTAhZuvrNXhYgBFSssHX2g_15m4KeaOd3lnTTDbPNut41-ghgl_kb22qx9mbvBBurK6tNxF0sn5df4WL7-RYsPTIGzjSnNPL6tmoXYJXh_2s-nn56cfFl-b62-eri_PrxjDe5ob0WoLsEUeDppJz2ZmWj4BAc40H1As9yJ4J1gIaTUeMafvR9AZzJgSwHtOz6u1ed3IhqcMTJ4VlhwRhknQFcbVHDEFv1RTtrhhVQVv1txDiWunyTMaBkqwzhg5oHDrCCJaSYjACGzlAGZO3Revjodvc72Aw4HPU7pHo4xtvN2odbhQjVNBOFIH3B4EYfs2QstrZZMCV34Iwl7lbIpBAki_O3v0D_b87tkeZGFKKMD4Mg5FaYnfPUkvs1CF2hfbm2MgD6T5n9A-EjNx8</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1980724928</pqid></control><display><type>article</type><title>Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Gangisetty, Omkaram ; Bekdash, Rola ; Maglakelidze, George ; Sarkar, Dipak K</creator><contributor>Homberg, Judith</contributor><creatorcontrib>Gangisetty, Omkaram ; Bekdash, Rola ; Maglakelidze, George ; Sarkar, Dipak K ; Homberg, Judith</creatorcontrib><description>Proopiomelanocortin (POMC) is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA) axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2) in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA) axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC) of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH) gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH) and corticosterone hormone responses to lipopolysaccharide (LPS) challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113228</identifier><identifier>PMID: 25409090</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adrenocorticotropic hormone ; Alcohol use ; Alcoholic beverages ; Animals ; Arcuate nucleus ; Arcuate Nucleus of Hypothalamus - metabolism ; Biology and Life Sciences ; Corticosterone ; Corticotropin-releasing hormone ; CpG islands ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epigenetics ; Ethanol ; Ethanol - adverse effects ; Exposure ; Female ; Gene expression ; Gene Expression Regulation ; Hypothalamic-pituitary-adrenal axis ; Hypothalamo-Hypophyseal System - metabolism ; Hypothalamus ; Lipopolysaccharides ; Male ; MeCP2 protein ; Methyl-CpG binding protein ; Methyl-CpG-Binding Protein 2 - metabolism ; Nuclei (cytology) ; Pituitary ; Pituitary-Adrenal System - metabolism ; Plasmids ; Pregnancy ; Prenatal Exposure Delayed Effects - chemically induced ; Prenatal Exposure Delayed Effects - genetics ; Prenatal Exposure Delayed Effects - metabolism ; Pro-Opiomelanocortin - genetics ; Pro-Opiomelanocortin - metabolism ; Promoter Regions, Genetic ; Proopiomelanocortin ; Rats ; Rats, Sprague-Dawley ; Rodents ; Transcription ; Ventricle ; Ventricles (cerebral)</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113228-e113228</ispartof><rights>2014 Gangisetty et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Gangisetty et al 2014 Gangisetty et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-2ba9e9b050da395598c65fe0ea5a1d0b7ad9b4746e0fc82cc6bfcbc15477e4b13</citedby><cites>FETCH-LOGICAL-c456t-2ba9e9b050da395598c65fe0ea5a1d0b7ad9b4746e0fc82cc6bfcbc15477e4b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237387/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237387/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25409090$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Homberg, Judith</contributor><creatorcontrib>Gangisetty, Omkaram</creatorcontrib><creatorcontrib>Bekdash, Rola</creatorcontrib><creatorcontrib>Maglakelidze, George</creatorcontrib><creatorcontrib>Sarkar, Dipak K</creatorcontrib><title>Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Proopiomelanocortin (POMC) is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA) axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2) in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA) axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC) of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH) gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH) and corticosterone hormone responses to lipopolysaccharide (LPS) challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.</description><subject>Adrenocorticotropic hormone</subject><subject>Alcohol use</subject><subject>Alcoholic beverages</subject><subject>Animals</subject><subject>Arcuate nucleus</subject><subject>Arcuate Nucleus of Hypothalamus - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Corticosterone</subject><subject>Corticotropin-releasing hormone</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenetics</subject><subject>Ethanol</subject><subject>Ethanol - adverse effects</subject><subject>Exposure</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Hypothalamic-pituitary-adrenal axis</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Hypothalamus</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>MeCP2 protein</subject><subject>Methyl-CpG binding protein</subject><subject>Methyl-CpG-Binding Protein 2 - metabolism</subject><subject>Nuclei (cytology)</subject><subject>Pituitary</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>Plasmids</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects - chemically induced</subject><subject>Prenatal Exposure Delayed Effects - genetics</subject><subject>Prenatal Exposure Delayed Effects - metabolism</subject><subject>Pro-Opiomelanocortin - genetics</subject><subject>Pro-Opiomelanocortin - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Proopiomelanocortin</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Transcription</subject><subject>Ventricle</subject><subject>Ventricles (cerebral)</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAUjBCIlsI_QBCJC5cs_ozjC1JVUahUBAc4W47zsuuV1w62U7V_iN-Jw26rLUI-2HqemffGnqp6jdEKU4E_bMMcvXarKXhYIYwpId2T6hRLSpqWIPr06HxSvUhpixCnXds-r04IZ0iWdVr9voSsXa2dCZvgaridQpojlEKGmOophjDZsAOnfTAhZuvrNXhYgBFSssHX2g_15m4KeaOd3lnTTDbPNut41-ghgl_kb22qx9mbvBBurK6tNxF0sn5df4WL7-RYsPTIGzjSnNPL6tmoXYJXh_2s-nn56cfFl-b62-eri_PrxjDe5ob0WoLsEUeDppJz2ZmWj4BAc40H1As9yJ4J1gIaTUeMafvR9AZzJgSwHtOz6u1ed3IhqcMTJ4VlhwRhknQFcbVHDEFv1RTtrhhVQVv1txDiWunyTMaBkqwzhg5oHDrCCJaSYjACGzlAGZO3Revjodvc72Aw4HPU7pHo4xtvN2odbhQjVNBOFIH3B4EYfs2QstrZZMCV34Iwl7lbIpBAki_O3v0D_b87tkeZGFKKMD4Mg5FaYnfPUkvs1CF2hfbm2MgD6T5n9A-EjNx8</recordid><startdate>20141119</startdate><enddate>20141119</enddate><creator>Gangisetty, Omkaram</creator><creator>Bekdash, Rola</creator><creator>Maglakelidze, George</creator><creator>Sarkar, Dipak K</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141119</creationdate><title>Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus</title><author>Gangisetty, Omkaram ; Bekdash, Rola ; Maglakelidze, George ; Sarkar, Dipak K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-2ba9e9b050da395598c65fe0ea5a1d0b7ad9b4746e0fc82cc6bfcbc15477e4b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adrenocorticotropic hormone</topic><topic>Alcohol use</topic><topic>Alcoholic beverages</topic><topic>Animals</topic><topic>Arcuate nucleus</topic><topic>Arcuate Nucleus of Hypothalamus - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Corticosterone</topic><topic>Corticotropin-releasing hormone</topic><topic>CpG islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epigenetics</topic><topic>Ethanol</topic><topic>Ethanol - adverse effects</topic><topic>Exposure</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Hypothalamic-pituitary-adrenal axis</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>Hypothalamus</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>MeCP2 protein</topic><topic>Methyl-CpG binding protein</topic><topic>Methyl-CpG-Binding Protein 2 - metabolism</topic><topic>Nuclei (cytology)</topic><topic>Pituitary</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>Plasmids</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects - chemically induced</topic><topic>Prenatal Exposure Delayed Effects - genetics</topic><topic>Prenatal Exposure Delayed Effects - metabolism</topic><topic>Pro-Opiomelanocortin - genetics</topic><topic>Pro-Opiomelanocortin - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Proopiomelanocortin</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Transcription</topic><topic>Ventricle</topic><topic>Ventricles (cerebral)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gangisetty, Omkaram</creatorcontrib><creatorcontrib>Bekdash, Rola</creatorcontrib><creatorcontrib>Maglakelidze, George</creatorcontrib><creatorcontrib>Sarkar, Dipak K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gangisetty, Omkaram</au><au>Bekdash, Rola</au><au>Maglakelidze, George</au><au>Sarkar, Dipak K</au><au>Homberg, Judith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-19</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113228</spage><epage>e113228</epage><pages>e113228-e113228</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Proopiomelanocortin (POMC) is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA) axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2) in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA) axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC) of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH) gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH) and corticosterone hormone responses to lipopolysaccharide (LPS) challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25409090</pmid><doi>10.1371/journal.pone.0113228</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2014-11, Vol.9 (11), p.e113228-e113228
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1980724928
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry
subjects Adrenocorticotropic hormone
Alcohol use
Alcoholic beverages
Animals
Arcuate nucleus
Arcuate Nucleus of Hypothalamus - metabolism
Biology and Life Sciences
Corticosterone
Corticotropin-releasing hormone
CpG islands
Deoxyribonucleic acid
DNA
DNA Methylation
Epigenetics
Ethanol
Ethanol - adverse effects
Exposure
Female
Gene expression
Gene Expression Regulation
Hypothalamic-pituitary-adrenal axis
Hypothalamo-Hypophyseal System - metabolism
Hypothalamus
Lipopolysaccharides
Male
MeCP2 protein
Methyl-CpG binding protein
Methyl-CpG-Binding Protein 2 - metabolism
Nuclei (cytology)
Pituitary
Pituitary-Adrenal System - metabolism
Plasmids
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced
Prenatal Exposure Delayed Effects - genetics
Prenatal Exposure Delayed Effects - metabolism
Pro-Opiomelanocortin - genetics
Pro-Opiomelanocortin - metabolism
Promoter Regions, Genetic
Proopiomelanocortin
Rats
Rats, Sprague-Dawley
Rodents
Transcription
Ventricle
Ventricles (cerebral)
title Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T16%3A25%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fetal%20alcohol%20exposure%20alters%20proopiomelanocortin%20gene%20expression%20and%20hypothalamic-pituitary-adrenal%20axis%20function%20via%20increasing%20MeCP2%20expression%20in%20the%20hypothalamus&rft.jtitle=PloS%20one&rft.au=Gangisetty,%20Omkaram&rft.date=2014-11-19&rft.volume=9&rft.issue=11&rft.spage=e113228&rft.epage=e113228&rft.pages=e113228-e113228&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0113228&rft_dat=%3Cproquest_plos_%3E1980724928%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1980724928&rft_id=info:pmid/25409090&rft_doaj_id=oai_doaj_org_article_948cc3d0fd824219931ec71c9dea9e56&rfr_iscdi=true