Microglia engulf viable newborn cells in the epileptic dentate gyrus
Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microg...
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description | Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase‐negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508–1517
Main points
Status epilepticus‐induced newborn cells were rapidly eliminated.
Microglia rapidly engulfed viable newborn cells after status epilepticus.
Inhibition of microglia resulted in abnormal survival of newborn cells. |
doi_str_mv | 10.1002/glia.23018 |
format | Article |
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Main points
Status epilepticus‐induced newborn cells were rapidly eliminated.
Microglia rapidly engulfed viable newborn cells after status epilepticus.
Inhibition of microglia resulted in abnormal survival of newborn cells.</description><identifier>ISSN: 0894-1491</identifier><identifier>EISSN: 1098-1136</identifier><identifier>DOI: 10.1002/glia.23018</identifier><identifier>PMID: 27301702</identifier><identifier>CODEN: GLIAEJ</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Dentate Gyrus - metabolism ; epilepsy ; hippocampus ; Hippocampus - cytology ; Homeostasis - physiology ; Male ; Mice, Inbred C57BL ; microglia ; Microglia - metabolism ; Neural Stem Cells - metabolism ; neurogenesis ; Neurogenesis - physiology ; Neurons - metabolism ; phagocytosis ; Status Epilepticus - metabolism</subject><ispartof>Glia, 2016-09, Vol.64 (9), p.1508-1517</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4948-9c71f5a2abb20eee5562ba262d8e2b528bba73720467a0e517dae91e1562e9413</citedby><cites>FETCH-LOGICAL-c4948-9c71f5a2abb20eee5562ba262d8e2b528bba73720467a0e517dae91e1562e9413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fglia.23018$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fglia.23018$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27301702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Cong</creatorcontrib><creatorcontrib>Koyama, Ryuta</creatorcontrib><creatorcontrib>Ikegaya, Yuji</creatorcontrib><title>Microglia engulf viable newborn cells in the epileptic dentate gyrus</title><title>Glia</title><addtitle>Glia</addtitle><description>Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase‐negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508–1517
Main points
Status epilepticus‐induced newborn cells were rapidly eliminated.
Microglia rapidly engulfed viable newborn cells after status epilepticus.
Inhibition of microglia resulted in abnormal survival of newborn cells.</description><subject>Animals</subject><subject>Dentate Gyrus - metabolism</subject><subject>epilepsy</subject><subject>hippocampus</subject><subject>Hippocampus - cytology</subject><subject>Homeostasis - physiology</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>microglia</subject><subject>Microglia - metabolism</subject><subject>Neural Stem Cells - metabolism</subject><subject>neurogenesis</subject><subject>Neurogenesis - physiology</subject><subject>Neurons - metabolism</subject><subject>phagocytosis</subject><subject>Status Epilepticus - metabolism</subject><issn>0894-1491</issn><issn>1098-1136</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0UFP2zAUB3BrAo0OdtkHmCztMiGl-DlObB9RB6VTgUunSbtYdvpazNKk2Ams334uBQ4cECfL0u_9Zf8fIV-ADYExfrKsvR3ynIH6QAbAtMoA8nKPDJjSIgOh4YB8ivGWMUgX-ZEccJm0ZHxAflz6KrTbBIrNsq8X9N5bVyNt8MG1oaEV1nWkvqHdDVJc-xrXna_oHJvOdkiXm9DHI7K_sHXEz0_nIfl1fjYbXWTT6_FkdDrNKqGFynQlYVFYbp3jDBGLouTO8pLPFXJXcOWclbnkTJTSMixAzi1qQEgOtYD8kHzf5a5De9dj7MzKx-0DbYNtHw0oAKWV4OIdlJWlYHnJE_32it62fWjSRx4VU0oXMqnjnUp1xRhwYdbBr2zYGGBmuwazLdE8riHhr0-RvVvh_IU-954A7MBDKnTzRpQZTyenz6HZbsbHDv-9zNjw15SptsL8vhob_ufn7GJ0OTMi_w-GWp9Q</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Luo, Cong</creator><creator>Koyama, Ryuta</creator><creator>Ikegaya, Yuji</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201609</creationdate><title>Microglia engulf viable newborn cells in the epileptic dentate gyrus</title><author>Luo, Cong ; Koyama, Ryuta ; Ikegaya, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4948-9c71f5a2abb20eee5562ba262d8e2b528bba73720467a0e517dae91e1562e9413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Dentate Gyrus - metabolism</topic><topic>epilepsy</topic><topic>hippocampus</topic><topic>Hippocampus - cytology</topic><topic>Homeostasis - physiology</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>microglia</topic><topic>Microglia - metabolism</topic><topic>Neural Stem Cells - metabolism</topic><topic>neurogenesis</topic><topic>Neurogenesis - physiology</topic><topic>Neurons - metabolism</topic><topic>phagocytosis</topic><topic>Status Epilepticus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Cong</creatorcontrib><creatorcontrib>Koyama, Ryuta</creatorcontrib><creatorcontrib>Ikegaya, Yuji</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Glia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Cong</au><au>Koyama, Ryuta</au><au>Ikegaya, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microglia engulf viable newborn cells in the epileptic dentate gyrus</atitle><jtitle>Glia</jtitle><addtitle>Glia</addtitle><date>2016-09</date><risdate>2016</risdate><volume>64</volume><issue>9</issue><spage>1508</spage><epage>1517</epage><pages>1508-1517</pages><issn>0894-1491</issn><eissn>1098-1136</eissn><coden>GLIAEJ</coden><abstract>Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase‐negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508–1517
Main points
Status epilepticus‐induced newborn cells were rapidly eliminated.
Microglia rapidly engulfed viable newborn cells after status epilepticus.
Inhibition of microglia resulted in abnormal survival of newborn cells.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>27301702</pmid><doi>10.1002/glia.23018</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Dentate Gyrus - metabolism epilepsy hippocampus Hippocampus - cytology Homeostasis - physiology Male Mice, Inbred C57BL microglia Microglia - metabolism Neural Stem Cells - metabolism neurogenesis Neurogenesis - physiology Neurons - metabolism phagocytosis Status Epilepticus - metabolism |
title | Microglia engulf viable newborn cells in the epileptic dentate gyrus |
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