C-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice
► Enhancement of functional recovery by inhibiting JNK after SCI. ► Cell death signal JNK induces axonal degeneration. ► Our data suggest importance of axonal dieback in the pathophysiology of CNS. C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and...
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| Veröffentlicht in: | Neuroscience research 2011-11, Vol.71 (3), p.266-277 |
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| creator | Yoshimura, Kazuhiro Ueno, Masaki Lee, Sachiko Nakamura, Yuka Sato, Akinobu Yoshimura, Koichi Kishima, Haruhiko Yoshimine, Toshiki Yamashita, Toshihide |
| description | ► Enhancement of functional recovery by inhibiting JNK after SCI. ► Cell death signal JNK induces axonal degeneration. ► Our data suggest importance of axonal dieback in the pathophysiology of CNS.
C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In
Jnk1
−/− and
Jnk3
−/− mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI. |
| doi_str_mv | 10.1016/j.neures.2011.07.1830 |
| format | Article |
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C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In
Jnk1
−/− and
Jnk3
−/− mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.</description><identifier>ISSN: 0168-0102</identifier><identifier>EISSN: 1872-8111</identifier><identifier>DOI: 10.1016/j.neures.2011.07.1830</identifier><identifier>PMID: 21824499</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Anthracenes - administration & dosage ; Axon degeneration ; Disease Models, Animal ; Female ; JNK ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitogen-Activated Protein Kinase 10 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 10 - deficiency ; Mitogen-Activated Protein Kinase 10 - genetics ; Mitogen-Activated Protein Kinase 8 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 8 - deficiency ; Mitogen-Activated Protein Kinase 8 - physiology ; Nerve Regeneration - drug effects ; Nerve Regeneration - genetics ; Paralysis - enzymology ; Paralysis - genetics ; Paralysis - physiopathology ; Recovery of Function - drug effects ; Recovery of Function - genetics ; Spinal Cord Injuries - enzymology ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; Spinal cord injury ; Wallerian Degeneration - enzymology ; Wallerian Degeneration - pathology ; Wallerian Degeneration - physiopathology</subject><ispartof>Neuroscience research, 2011-11, Vol.71 (3), p.266-277</ispartof><rights>2011 Elsevier Ireland Ltd and the Japan Neuroscience Society</rights><rights>Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-7c61e6cd0b7c8caadc4e149546d567747216bec031093d959dd87437ec6338c03</citedby><cites>FETCH-LOGICAL-c420t-7c61e6cd0b7c8caadc4e149546d567747216bec031093d959dd87437ec6338c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neures.2011.07.1830$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21824499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshimura, Kazuhiro</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Lee, Sachiko</creatorcontrib><creatorcontrib>Nakamura, Yuka</creatorcontrib><creatorcontrib>Sato, Akinobu</creatorcontrib><creatorcontrib>Yoshimura, Koichi</creatorcontrib><creatorcontrib>Kishima, Haruhiko</creatorcontrib><creatorcontrib>Yoshimine, Toshiki</creatorcontrib><creatorcontrib>Yamashita, Toshihide</creatorcontrib><title>C-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice</title><title>Neuroscience research</title><addtitle>Neurosci Res</addtitle><description>► Enhancement of functional recovery by inhibiting JNK after SCI. ► Cell death signal JNK induces axonal degeneration. ► Our data suggest importance of axonal dieback in the pathophysiology of CNS.
C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In
Jnk1
−/− and
Jnk3
−/− mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.</description><subject>Animals</subject><subject>Anthracenes - administration & dosage</subject><subject>Axon degeneration</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>JNK</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mitogen-Activated Protein Kinase 10 - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase 10 - deficiency</subject><subject>Mitogen-Activated Protein Kinase 10 - genetics</subject><subject>Mitogen-Activated Protein Kinase 8 - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase 8 - deficiency</subject><subject>Mitogen-Activated Protein Kinase 8 - physiology</subject><subject>Nerve Regeneration - drug effects</subject><subject>Nerve Regeneration - genetics</subject><subject>Paralysis - enzymology</subject><subject>Paralysis - genetics</subject><subject>Paralysis - physiopathology</subject><subject>Recovery of Function - drug effects</subject><subject>Recovery of Function - genetics</subject><subject>Spinal Cord Injuries - enzymology</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal cord injury</subject><subject>Wallerian Degeneration - enzymology</subject><subject>Wallerian Degeneration - pathology</subject><subject>Wallerian Degeneration - physiopathology</subject><issn>0168-0102</issn><issn>1872-8111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFu1DAQhi0EotvCI4B845TgsZPYPqFqVSioggucLa89i7wk9mInK_r2OGzhWi62NPPNP9J8hLwC1gKD4e2hjbhkLC1nAC2TLSjBnpANKMkbBQBPyaZyqmHA-AW5LOXAGBO6E8_JBQfFu07rDYnb5tMS6edmxjyFaEf6o74FaYh-cVio_ZXWqsfvGDHbOaRIbfR0DFOYC53SnDLN6NIJ8z21-5pDy_FPkkvZ15zDUhsh0ik4fEGe7e1Y8OXDf0W-vb_5ur1t7r58-Li9vmtcx9ncSDcADs6znXTKWetdh9Dpvht8P0jZSQ7DDh0TwLTwutfeK9kJiW4QQtX6FXlzzj3m9HPBMpspFIfjaCOmpRilNfSCc_kfZK960euV7M-ky6mUjHtzzGGy-d4AM6sTczBnJ2Z1Ypg0q5M69_phw7Kb0P-b-iuhAu_OANaLnAJmU1zA6NCHetjZ-BQeWfEbaa-gLA</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Yoshimura, Kazuhiro</creator><creator>Ueno, Masaki</creator><creator>Lee, Sachiko</creator><creator>Nakamura, Yuka</creator><creator>Sato, Akinobu</creator><creator>Yoshimura, Koichi</creator><creator>Kishima, Haruhiko</creator><creator>Yoshimine, Toshiki</creator><creator>Yamashita, Toshihide</creator><general>Elsevier Ireland Ltd</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>20111101</creationdate><title>C-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice</title><author>Yoshimura, Kazuhiro ; Ueno, Masaki ; Lee, Sachiko ; Nakamura, Yuka ; Sato, Akinobu ; Yoshimura, Koichi ; Kishima, Haruhiko ; Yoshimine, Toshiki ; Yamashita, Toshihide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-7c61e6cd0b7c8caadc4e149546d567747216bec031093d959dd87437ec6338c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Anthracenes - administration & dosage</topic><topic>Axon degeneration</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>JNK</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mitogen-Activated Protein Kinase 10 - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase 10 - deficiency</topic><topic>Mitogen-Activated Protein Kinase 10 - genetics</topic><topic>Mitogen-Activated Protein Kinase 8 - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase 8 - deficiency</topic><topic>Mitogen-Activated Protein Kinase 8 - physiology</topic><topic>Nerve Regeneration - drug effects</topic><topic>Nerve Regeneration - genetics</topic><topic>Paralysis - enzymology</topic><topic>Paralysis - genetics</topic><topic>Paralysis - physiopathology</topic><topic>Recovery of Function - drug effects</topic><topic>Recovery of Function - genetics</topic><topic>Spinal Cord Injuries - enzymology</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal cord injury</topic><topic>Wallerian Degeneration - enzymology</topic><topic>Wallerian Degeneration - pathology</topic><topic>Wallerian Degeneration - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshimura, Kazuhiro</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Lee, Sachiko</creatorcontrib><creatorcontrib>Nakamura, Yuka</creatorcontrib><creatorcontrib>Sato, Akinobu</creatorcontrib><creatorcontrib>Yoshimura, Koichi</creatorcontrib><creatorcontrib>Kishima, Haruhiko</creatorcontrib><creatorcontrib>Yoshimine, Toshiki</creatorcontrib><creatorcontrib>Yamashita, Toshihide</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshimura, Kazuhiro</au><au>Ueno, Masaki</au><au>Lee, Sachiko</au><au>Nakamura, Yuka</au><au>Sato, Akinobu</au><au>Yoshimura, Koichi</au><au>Kishima, Haruhiko</au><au>Yoshimine, Toshiki</au><au>Yamashita, Toshihide</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice</atitle><jtitle>Neuroscience research</jtitle><addtitle>Neurosci Res</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>71</volume><issue>3</issue><spage>266</spage><epage>277</epage><pages>266-277</pages><issn>0168-0102</issn><eissn>1872-8111</eissn><abstract>► Enhancement of functional recovery by inhibiting JNK after SCI. ► Cell death signal JNK induces axonal degeneration. ► Our data suggest importance of axonal dieback in the pathophysiology of CNS.
C-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In
Jnk1
−/− and
Jnk3
−/− mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>21824499</pmid><doi>10.1016/j.neures.2011.07.1830</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Anthracenes - administration & dosage Axon degeneration Disease Models, Animal Female JNK Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinase 10 - antagonists & inhibitors Mitogen-Activated Protein Kinase 10 - deficiency Mitogen-Activated Protein Kinase 10 - genetics Mitogen-Activated Protein Kinase 8 - antagonists & inhibitors Mitogen-Activated Protein Kinase 8 - deficiency Mitogen-Activated Protein Kinase 8 - physiology Nerve Regeneration - drug effects Nerve Regeneration - genetics Paralysis - enzymology Paralysis - genetics Paralysis - physiopathology Recovery of Function - drug effects Recovery of Function - genetics Spinal Cord Injuries - enzymology Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Spinal cord injury Wallerian Degeneration - enzymology Wallerian Degeneration - pathology Wallerian Degeneration - physiopathology |
| title | C-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice |
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