Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6/1 mice
Huntington's disease is a neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene which produces widespread neuronal and glial pathology. We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glia...
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| Veröffentlicht in: | PloS one 2013-09, Vol.8 (9), p.e73120-e73120 |
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| creator | Perucho, Juan Casarejos, Maria José Gómez, Ana Ruíz, Carolina Fernández-Estevez, Maria Ángeles Muñoz, Maria Paz de Yébenes, Justo García Mena, Maria Ángeles |
| description | Huntington's disease is a neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene which produces widespread neuronal and glial pathology. We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. These results suggest that CGM should be further explored as a putative neuroprotective agent in Huntington's disease. |
| doi_str_mv | 10.1371/journal.pone.0073120 |
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We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. These results suggest that CGM should be further explored as a putative neuroprotective agent in Huntington's disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0073120</identifier><identifier>PMID: 24069174</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal cognition ; Animals ; Augmentation ; Autophagy ; Brain ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; Cell death ; Cells, Cultured ; Cerebral cortex ; Cerebrospinal fluid ; Conditioning ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Culture Media, Conditioned - chemistry ; DARPP-32 protein ; Deoxyribonucleic acid ; DNA ; Dopamine ; Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics ; Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism ; Fetuses ; Genotype ; Genotype & phenotype ; Health aspects ; Humans ; Huntingtin ; Huntington Disease - drug therapy ; Huntington Disease - metabolism ; Huntington Disease - pathology ; Huntington's disease ; Huntingtons disease ; LAMP-2 protein ; Male ; Mice ; Neostriatum ; Neostriatum - drug effects ; Neostriatum - metabolism ; Nervous system diseases ; Neurobiology ; Neurodegenerative diseases ; Neuroglia - cytology ; Neuronal-glial interactions ; Neurons ; Neuroprotection ; Neurosciences ; Pathology ; Phagocytosis ; Polyglutamine ; Rodents ; Substantia nigra ; Substrates ; Trinucleotide repeats</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e73120-e73120</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Perucho 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. 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We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. 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drug therapy</subject><subject>Huntington Disease - metabolism</subject><subject>Huntington Disease - pathology</subject><subject>Huntington's disease</subject><subject>Huntingtons disease</subject><subject>LAMP-2 protein</subject><subject>Male</subject><subject>Mice</subject><subject>Neostriatum</subject><subject>Neostriatum - drug effects</subject><subject>Neostriatum - metabolism</subject><subject>Nervous system diseases</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neuroglia - cytology</subject><subject>Neuronal-glial interactions</subject><subject>Neurons</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Pathology</subject><subject>Phagocytosis</subject><subject>Polyglutamine</subject><subject>Rodents</subject><subject>Substantia nigra</subject><subject>Substrates</subject><subject>Trinucleotide repeats</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoMo7jr6D0QLgujFzOajTdIbYVn8GFhYcNULb0ImH22GtBmbVNx_b2anu0xlL6S0KSfPeZO8JweAlwiuEGHobBvGoZd-tQu9WUHICMLwEThFNcFLiiF5fPR_Ap7FuIWwIpzSp-AEl5DWiJWn4Od1GpxM0heut2N0oS-CLRrvckSFXruUQ0YXndFu7ArtOte72JpYtGOfXN_kt9jJ1AYfmpssUgz0DBWdU-Y5eGKlj-bFNC7A908fv118WV5efV5fnF8uFat4WhqtlYIEcsqIYqrWBkHDuNaWaovgRsmqQhWSClPLMadIS1pbzI2xNVeVJgvw-qC78yGKyZYoUEkwIrSsq0ysD4QOcit2g-vkcCOCdOI2EIZGyCE55Y2QUBuMsd5YXpWWc8nLGlYVrLLBJVE4a32YVhs32RRl-jRIPxOdz_SuFU34LQhjqM61WIB3k8AQfo0mJtG5qIz3sjdhvN139gVSwjL65h_04dNNVCPzAXIZQ15X7UXFeck4gZDm7wKsHqDyo00uVq6xdTk-S3g_S8hMMn9SI8cYxfr66_-zVz_m7NsjtjXSpzYGP-4vWpyD5QFUQ4hxMPbeZATFvgXu3BD7FhBTC-S0V8cFuk-6u_PkL4ifATE</recordid><startdate>20130912</startdate><enddate>20130912</enddate><creator>Perucho, Juan</creator><creator>Casarejos, Maria José</creator><creator>Gómez, Ana</creator><creator>Ruíz, Carolina</creator><creator>Fernández-Estevez, Maria Ángeles</creator><creator>Muñoz, Maria Paz</creator><creator>de Yébenes, Justo García</creator><creator>Mena, Maria Ángeles</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>20130912</creationdate><title>Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6/1 mice</title><author>Perucho, Juan ; Casarejos, Maria José ; Gómez, Ana ; Ruíz, Carolina ; Fernández-Estevez, Maria Ángeles ; Muñoz, Maria Paz ; de Yébenes, Justo García ; Mena, Maria Ángeles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-eddcc0308673c7c9de10e78ddf6df10bca55151ac26f82861da69f28eef98c5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal cognition</topic><topic>Animals</topic><topic>Augmentation</topic><topic>Autophagy</topic><topic>Brain</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - 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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>Perucho, Juan</au><au>Casarejos, Maria José</au><au>Gómez, Ana</au><au>Ruíz, Carolina</au><au>Fernández-Estevez, Maria Ángeles</au><au>Muñoz, Maria Paz</au><au>de Yébenes, Justo García</au><au>Mena, Maria Ángeles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6/1 mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-09-12</date><risdate>2013</risdate><volume>8</volume><issue>9</issue><spage>e73120</spage><epage>e73120</epage><pages>e73120-e73120</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Huntington's disease is a neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene which produces widespread neuronal and glial pathology. We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. These results suggest that CGM should be further explored as a putative neuroprotective agent in Huntington's disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24069174</pmid><doi>10.1371/journal.pone.0073120</doi><tpages>e73120</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-09, Vol.8 (9), p.e73120-e73120 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1432136495 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal cognition Animals Augmentation Autophagy Brain Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Cell death Cells, Cultured Cerebral cortex Cerebrospinal fluid Conditioning Corpus Striatum - drug effects Corpus Striatum - metabolism Culture Media, Conditioned - chemistry DARPP-32 protein Deoxyribonucleic acid DNA Dopamine Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism Fetuses Genotype Genotype & phenotype Health aspects Humans Huntingtin Huntington Disease - drug therapy Huntington Disease - metabolism Huntington Disease - pathology Huntington's disease Huntingtons disease LAMP-2 protein Male Mice Neostriatum Neostriatum - drug effects Neostriatum - metabolism Nervous system diseases Neurobiology Neurodegenerative diseases Neuroglia - cytology Neuronal-glial interactions Neurons Neuroprotection Neurosciences Pathology Phagocytosis Polyglutamine Rodents Substantia nigra Substrates Trinucleotide repeats |
| title | Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6/1 mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T05%3A19%3A45IST&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=Striatal%20infusion%20of%20glial%20conditioned%20medium%20diminishes%20huntingtin%20pathology%20in%20r6/1%20mice&rft.jtitle=PloS%20one&rft.au=Perucho,%20Juan&rft.date=2013-09-12&rft.volume=8&rft.issue=9&rft.spage=e73120&rft.epage=e73120&rft.pages=e73120-e73120&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0073120&rft_dat=%3Cgale_plos_%3EA478300678%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=1432136495&rft_id=info:pmid/24069174&rft_galeid=A478300678&rft_doaj_id=oai_doaj_org_article_a0de222dbf854f88a8490550507343c2&rfr_iscdi=true |