RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats
Aim: To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia. Methods: Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxicall...
Gespeichert in:
| Veröffentlicht in: | Acta pharmacologica Sinica 2009-07, Vol.30 (7), p.919-927 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 927 |
|---|---|
| container_issue | 7 |
| container_start_page | 919 |
| container_title | Acta pharmacologica Sinica |
| container_volume | 30 |
| creator | Zheng, Yong-qiu Liu, Jian-xun Li, Xin-zhi Xu, Li Xu, Yong-gang |
| description | Aim:
To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia.
Methods:
Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclin1 RNAi.
Results:
On the 14th day after MCAO, Beclin1 downregulation by RNAi increased the population of neural progenitor cells (BrdU
+
-DCX
+
), newborn immature cells (BrdU
+
-Tuj-1
+
) and mature neurons (BrdU
+
-MAP-2
+
), and reduced the apoptosis of immature neurons (caspase-3
+
-DCX
+
and caspase-3
+
-Tuj-1
+
) surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1 decreased infarct volume and inhibited histological injury and neurological deficits.
Conclusion:
RNAi-mediated downregulation of Beclin1 improves outcomes after transient MCAO. |
| doi_str_mv | 10.1038/aps.2009.79 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4006642</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1775390451</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-274d601961271da6c91b095443b4156298de92cc6740f67178c9472df3a412383</originalsourceid><addsrcrecordid>eNp9kdFrFDEQxoNYbK0--S6LD_pg98wk2WTzItSiVSgKos8hl5295thLziSr9L835x2tivg0gfnlm_nmI-QJ0AVQ3r-y27xglOqF0vfICSjRtYp14n59SwWtoD0_Jg9zXlPKGQf9gByD7pTQuj8h5vPH88aHgmnEhMFhu8HB24JDM8QfIeFqnmzxMTRxbN6gm3yAxpaCYa5Qblz9tUx2anx217jxroqt53RTS5NsyY_I0WinjI8P9ZR8fff2y8X79urT5YeL86vWdQJKy5QYJAUtgSkYrHQallR3QvClgE4y3Q-omXNSCTpWV6p3Wig2jNwKYLznp-T1Xnc7L6sDh6HUrcw2-Y1NNyZab_7sBH9tVvG7EZRKKVgVeHEQSPHbjLmYTbWE02QDxjkbxTmXXMFu1PP_koxqzsWvnZ79Ba7jnEI9g2HAqehkBxV6uYdcijknHG93Bmp2-Zqar9nla5Su9NPfbd6xh0ArcLYHcm2FFaa7mf_S-wmfCa9s</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213045651</pqid></control><display><type>article</type><title>RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Zheng, Yong-qiu ; Liu, Jian-xun ; Li, Xin-zhi ; Xu, Li ; Xu, Yong-gang</creator><creatorcontrib>Zheng, Yong-qiu ; Liu, Jian-xun ; Li, Xin-zhi ; Xu, Li ; Xu, Yong-gang</creatorcontrib><description>Aim:
To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia.
Methods:
Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclin1 RNAi.
Results:
On the 14th day after MCAO, Beclin1 downregulation by RNAi increased the population of neural progenitor cells (BrdU
+
-DCX
+
), newborn immature cells (BrdU
+
-Tuj-1
+
) and mature neurons (BrdU
+
-MAP-2
+
), and reduced the apoptosis of immature neurons (caspase-3
+
-DCX
+
and caspase-3
+
-Tuj-1
+
) surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1 decreased infarct volume and inhibited histological injury and neurological deficits.
Conclusion:
RNAi-mediated downregulation of Beclin1 improves outcomes after transient MCAO.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2009.79</identifier><identifier>PMID: 19574998</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis - physiology ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Beclin-1 ; Behavior, Animal - physiology ; Biomedical and Life Sciences ; Biomedicine ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cell Differentiation - physiology ; Doublecortin Protein ; Down-Regulation ; Immunology ; Infarction, Middle Cerebral Artery ; Internal Medicine ; Lateral Ventricles - metabolism ; Male ; Medical Microbiology ; Neurons - cytology ; Neurons - metabolism ; Original ; original-article ; Pharmacology/Toxicology ; Rats ; Rats, Sprague-Dawley ; RNA Interference ; Stem Cells - metabolism ; Vaccine</subject><ispartof>Acta pharmacologica Sinica, 2009-07, Vol.30 (7), p.919-927</ispartof><rights>CPS and SIMM 2009</rights><rights>Copyright Nature Publishing Group Jul 2009</rights><rights>Copyright © 2009 CPS and SIMM 2009 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-274d601961271da6c91b095443b4156298de92cc6740f67178c9472df3a412383</citedby><cites>FETCH-LOGICAL-c541t-274d601961271da6c91b095443b4156298de92cc6740f67178c9472df3a412383</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/PMC4006642/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006642/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19574998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Yong-qiu</creatorcontrib><creatorcontrib>Liu, Jian-xun</creatorcontrib><creatorcontrib>Li, Xin-zhi</creatorcontrib><creatorcontrib>Xu, Li</creatorcontrib><creatorcontrib>Xu, Yong-gang</creatorcontrib><title>RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Aim:
To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia.
Methods:
Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclin1 RNAi.
Results:
On the 14th day after MCAO, Beclin1 downregulation by RNAi increased the population of neural progenitor cells (BrdU
+
-DCX
+
), newborn immature cells (BrdU
+
-Tuj-1
+
) and mature neurons (BrdU
+
-MAP-2
+
), and reduced the apoptosis of immature neurons (caspase-3
+
-DCX
+
and caspase-3
+
-Tuj-1
+
) surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1 decreased infarct volume and inhibited histological injury and neurological deficits.
Conclusion:
RNAi-mediated downregulation of Beclin1 improves outcomes after transient MCAO.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Beclin-1</subject><subject>Behavior, Animal - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cell Differentiation - physiology</subject><subject>Doublecortin Protein</subject><subject>Down-Regulation</subject><subject>Immunology</subject><subject>Infarction, Middle Cerebral Artery</subject><subject>Internal Medicine</subject><subject>Lateral Ventricles - metabolism</subject><subject>Male</subject><subject>Medical Microbiology</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Pharmacology/Toxicology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA Interference</subject><subject>Stem Cells - metabolism</subject><subject>Vaccine</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kdFrFDEQxoNYbK0--S6LD_pg98wk2WTzItSiVSgKos8hl5295thLziSr9L835x2tivg0gfnlm_nmI-QJ0AVQ3r-y27xglOqF0vfICSjRtYp14n59SwWtoD0_Jg9zXlPKGQf9gByD7pTQuj8h5vPH88aHgmnEhMFhu8HB24JDM8QfIeFqnmzxMTRxbN6gm3yAxpaCYa5Qblz9tUx2anx217jxroqt53RTS5NsyY_I0WinjI8P9ZR8fff2y8X79urT5YeL86vWdQJKy5QYJAUtgSkYrHQallR3QvClgE4y3Q-omXNSCTpWV6p3Wig2jNwKYLznp-T1Xnc7L6sDh6HUrcw2-Y1NNyZab_7sBH9tVvG7EZRKKVgVeHEQSPHbjLmYTbWE02QDxjkbxTmXXMFu1PP_koxqzsWvnZ79Ba7jnEI9g2HAqehkBxV6uYdcijknHG93Bmp2-Zqar9nla5Su9NPfbd6xh0ArcLYHcm2FFaa7mf_S-wmfCa9s</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Zheng, Yong-qiu</creator><creator>Liu, Jian-xun</creator><creator>Li, Xin-zhi</creator><creator>Xu, Li</creator><creator>Xu, Yong-gang</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7TM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090701</creationdate><title>RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats</title><author>Zheng, Yong-qiu ; Liu, Jian-xun ; Li, Xin-zhi ; Xu, Li ; Xu, Yong-gang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-274d601961271da6c91b095443b4156298de92cc6740f67178c9472df3a412383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apoptosis - physiology</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Beclin-1</topic><topic>Behavior, Animal - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Cell Differentiation - physiology</topic><topic>Doublecortin Protein</topic><topic>Down-Regulation</topic><topic>Immunology</topic><topic>Infarction, Middle Cerebral Artery</topic><topic>Internal Medicine</topic><topic>Lateral Ventricles - metabolism</topic><topic>Male</topic><topic>Medical Microbiology</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Pharmacology/Toxicology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA Interference</topic><topic>Stem Cells - metabolism</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Yong-qiu</creatorcontrib><creatorcontrib>Liu, Jian-xun</creatorcontrib><creatorcontrib>Li, Xin-zhi</creatorcontrib><creatorcontrib>Xu, Li</creatorcontrib><creatorcontrib>Xu, Yong-gang</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Yong-qiu</au><au>Liu, Jian-xun</au><au>Li, Xin-zhi</au><au>Xu, Li</au><au>Xu, Yong-gang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>30</volume><issue>7</issue><spage>919</spage><epage>927</epage><pages>919-927</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim:
To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia.
Methods:
Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector-associated RNA interference (RNAi) system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclin1 RNAi.
Results:
On the 14th day after MCAO, Beclin1 downregulation by RNAi increased the population of neural progenitor cells (BrdU
+
-DCX
+
), newborn immature cells (BrdU
+
-Tuj-1
+
) and mature neurons (BrdU
+
-MAP-2
+
), and reduced the apoptosis of immature neurons (caspase-3
+
-DCX
+
and caspase-3
+
-Tuj-1
+
) surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1 decreased infarct volume and inhibited histological injury and neurological deficits.
Conclusion:
RNAi-mediated downregulation of Beclin1 improves outcomes after transient MCAO.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19574998</pmid><doi>10.1038/aps.2009.79</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1671-4083 |
| ispartof | Acta pharmacologica Sinica, 2009-07, Vol.30 (7), p.919-927 |
| issn | 1671-4083 1745-7254 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4006642 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis - physiology Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Beclin-1 Behavior, Animal - physiology Biomedical and Life Sciences Biomedicine Brain Ischemia - metabolism Brain Ischemia - pathology Cell Differentiation - physiology Doublecortin Protein Down-Regulation Immunology Infarction, Middle Cerebral Artery Internal Medicine Lateral Ventricles - metabolism Male Medical Microbiology Neurons - cytology Neurons - metabolism Original original-article Pharmacology/Toxicology Rats Rats, Sprague-Dawley RNA Interference Stem Cells - metabolism Vaccine |
| title | RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic injury in rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T07%3A37%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=RNA%20interference-mediated%20downregulation%20of%20Beclin1%20attenuates%20cerebral%20ischemic%20injury%20in%20rats&rft.jtitle=Acta%20pharmacologica%20Sinica&rft.au=Zheng,%20Yong-qiu&rft.date=2009-07-01&rft.volume=30&rft.issue=7&rft.spage=919&rft.epage=927&rft.pages=919-927&rft.issn=1671-4083&rft.eissn=1745-7254&rft_id=info:doi/10.1038/aps.2009.79&rft_dat=%3Cproquest_pubme%3E1775390451%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213045651&rft_id=info:pmid/19574998&rfr_iscdi=true |