Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens
We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life e...
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| description | We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory. |
| doi_str_mv | 10.1371/journal.pone.0051385 |
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These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051385</identifier><identifier>PMID: 23240018</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>17β-Estradiol ; Acetyltransferase ; Aging ; Aging - genetics ; Aging - metabolism ; AKT protein ; Animals ; Biology ; Choline ; Choline O-acetyltransferase ; Cognition & reasoning ; Cognitive ability ; Comparative analysis ; Estradiol ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Estrogen receptors ; Estrogens ; Extracellular signal-regulated kinase ; Females ; Genetic Vectors ; Gerontology ; Hippocampus ; Hippocampus - metabolism ; Immunological memory ; Kinases ; MAP kinase ; Maze Learning ; Medicine ; Memory - drug effects ; Memory - physiology ; Memory tasks ; Menopause ; Mental task performance ; Mitogen-Activated Protein Kinases - metabolism ; Ovariectomy ; Phenols (Class of compounds) ; Phosphorylation ; Phosphotransferases ; Rats ; Rodents ; Sex hormones ; Spatial analysis ; Spatial memory ; Viruses ; Western blotting</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51385-e51385</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Witty et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2012 Witty et al 2012 Witty et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c2882063b9fe4dbd240e064524f45430831c162974e229d16c63cde10e4963ea3</citedby><cites>FETCH-LOGICAL-c692t-c2882063b9fe4dbd240e064524f45430831c162974e229d16c63cde10e4963ea3</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/PMC3519866/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519866/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23240018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Witty, Christine F</creatorcontrib><creatorcontrib>Foster, Thomas C</creatorcontrib><creatorcontrib>Semple-Rowland, Susan L</creatorcontrib><creatorcontrib>Daniel, Jill M</creatorcontrib><title>Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.</description><subject>17β-Estradiol</subject><subject>Acetyltransferase</subject><subject>Aging</subject><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Biology</subject><subject>Choline</subject><subject>Choline O-acetyltransferase</subject><subject>Cognition & reasoning</subject><subject>Cognitive ability</subject><subject>Comparative analysis</subject><subject>Estradiol</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Extracellular signal-regulated kinase</subject><subject>Females</subject><subject>Genetic Vectors</subject><subject>Gerontology</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Immunological memory</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Maze Learning</subject><subject>Medicine</subject><subject>Memory - drug effects</subject><subject>Memory - physiology</subject><subject>Memory tasks</subject><subject>Menopause</subject><subject>Mental task performance</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Ovariectomy</subject><subject>Phenols (Class of compounds)</subject><subject>Phosphorylation</subject><subject>Phosphotransferases</subject><subject>Rats</subject><subject>Rodents</subject><subject>Sex hormones</subject><subject>Spatial analysis</subject><subject>Spatial memory</subject><subject>Viruses</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uKFDEQhhtRXF19A9GAIHoxY059uhGWxcPAyoqn21CTru7O2pO0Sc_gPpTvaI0zu-zIXkgTOiRf_VX5k8qyJ4LPhSrF64uwjh6G-Rg8zjnPharyO9kDUSs5KyRXd2_Mj7KHKV0QpKqiuJ8dSSU156J6kP1eeBsRkvMd6904BgurEQaGaYqhQ88iWhynEBkMYw9swA0OiW0c0IgEbtDSbmJup4OJfTz5xH44T3MGdnIbmFzwDHzD0PfgLSErXIV4STEMum3mCNNWgU09xSwTEsRCy8IGogN_XUx6lN1rYUj4eP8_zr69e_v19MPs7Pz94vTkbGaLWk4zK6tK8kIt6xZ1s2zosMgLnUvd6lwrXilhRSHrUqOUdSMKWyjboOCo60IhqOPs2U53HEIye6eTEUqWQuVlUROx2BFNgAszRreCeGkCOPN3IcTOQJycHdCUqErUaklFKV1XJRQ8rwrQ3HItOC9J680-23q5wsain8jZA9HDHe9604WNUbmo6UJJ4OVeIIafa3LLrFyyOAzgMaypbqlqnutSVYQ-_we9_XR7qgM6gPNtoLx2K2pOdFmSgbUURM1voehrcOUsPcvW0fpBwKuDAGIm_DV1sE7JLL58_n_2_Psh--IG2yMMU5_CsN4-vHQI6h1oY0gpYnttsuBm21VXbphtV5l9V1HY05sXdB101UbqD-U7HgI</recordid><startdate>20121211</startdate><enddate>20121211</enddate><creator>Witty, Christine F</creator><creator>Foster, Thomas C</creator><creator>Semple-Rowland, Susan L</creator><creator>Daniel, Jill M</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>IOV</scope><scope>ISR</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>20121211</creationdate><title>Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens</title><author>Witty, Christine F ; Foster, Thomas C ; Semple-Rowland, Susan L ; Daniel, Jill M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c2882063b9fe4dbd240e064524f45430831c162974e229d16c63cde10e4963ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>17β-Estradiol</topic><topic>Acetyltransferase</topic><topic>Aging</topic><topic>Aging - 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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>Witty, Christine F</au><au>Foster, Thomas C</au><au>Semple-Rowland, Susan L</au><au>Daniel, Jill M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-11</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e51385</spage><epage>e51385</epage><pages>e51385-e51385</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23240018</pmid><doi>10.1371/journal.pone.0051385</doi><tpages>e51385</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 17β-Estradiol Acetyltransferase Aging Aging - genetics Aging - metabolism AKT protein Animals Biology Choline Choline O-acetyltransferase Cognition & reasoning Cognitive ability Comparative analysis Estradiol Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Estrogen receptors Estrogens Extracellular signal-regulated kinase Females Genetic Vectors Gerontology Hippocampus Hippocampus - metabolism Immunological memory Kinases MAP kinase Maze Learning Medicine Memory - drug effects Memory - physiology Memory tasks Menopause Mental task performance Mitogen-Activated Protein Kinases - metabolism Ovariectomy Phenols (Class of compounds) Phosphorylation Phosphotransferases Rats Rodents Sex hormones Spatial analysis Spatial memory Viruses Western blotting |
| title | Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T13%3A47%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increasing%20hippocampal%20estrogen%20receptor%20alpha%20levels%20via%20viral%20vectors%20increases%20MAP%20kinase%20activation%20and%20enhances%20memory%20in%20aging%20rats%20in%20the%20absence%20of%20ovarian%20estrogens&rft.jtitle=PloS%20one&rft.au=Witty,%20Christine%20F&rft.date=2012-12-11&rft.volume=7&rft.issue=12&rft.spage=e51385&rft.epage=e51385&rft.pages=e51385-e51385&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051385&rft_dat=%3Cgale_plos_%3EA477083921%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1327135769&rft_id=info:pmid/23240018&rft_galeid=A477083921&rft_doaj_id=oai_doaj_org_article_7e37e43b28834987a60586a40c041007&rfr_iscdi=true |