GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons
We previously demonstrated that coadministration of glial cell line‐derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was uncle...
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| Veröffentlicht in: | Glia 2009-08, Vol.57 (11), p.1178-1191 |
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| creator | Zhang, Liqun Ma, Zhengwen Smith, George M. Wen, Xuejun Pressman, Yelena Wood, Patrick M. Xu, Xiao-Ming |
| description | We previously demonstrated that coadministration of glial cell line‐derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC‐DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF‐enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/glia.20840 |
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However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC‐DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF‐enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley‐Liss, Inc.</description><identifier>ISSN: 0894-1491</identifier><identifier>EISSN: 1098-1136</identifier><identifier>DOI: 10.1002/glia.20840</identifier><identifier>PMID: 19170182</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; axon ; Axons - physiology ; Axons - ultrastructure ; Cell Count ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Female ; Ganglia, Spinal - physiology ; GDNF ; Glial Cell Line-Derived Neurotrophic Factor - metabolism ; Glial Cell Line-Derived Neurotrophic Factor - pharmacology ; Myelin Sheath - physiology ; myelination ; Nerve Fibers, Myelinated - physiology ; Nerve Fibers, Myelinated - ultrastructure ; Nerve Regeneration - drug effects ; Nerve Regeneration - physiology ; Neurites - physiology ; Neurons - drug effects ; Neurons - physiology ; Neurons - ultrastructure ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; regeneration ; Schwann cell ; Schwann Cells - physiology ; Schwann Cells - transplantation ; Sciatic Nerve - physiology ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - surgery ; Spinal Cord Injuries - therapy ; spinal cord injury</subject><ispartof>Glia, 2009-08, Vol.57 (11), p.1178-1191</ispartof><rights>Copyright © 2009 Wiley‐Liss, Inc.</rights><rights>2009 Wiley-Liss, Inc. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5540-6de658b951bb298a7c42ee04749ea4c0a7b0d77bfb8f77f9b3514718827c86e53</citedby><cites>FETCH-LOGICAL-c5540-6de658b951bb298a7c42ee04749ea4c0a7b0d77bfb8f77f9b3514718827c86e53</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.20840$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fglia.20840$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19170182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Liqun</creatorcontrib><creatorcontrib>Ma, Zhengwen</creatorcontrib><creatorcontrib>Smith, George M.</creatorcontrib><creatorcontrib>Wen, Xuejun</creatorcontrib><creatorcontrib>Pressman, Yelena</creatorcontrib><creatorcontrib>Wood, Patrick M.</creatorcontrib><creatorcontrib>Xu, Xiao-Ming</creatorcontrib><title>GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons</title><title>Glia</title><addtitle>Glia</addtitle><description>We previously demonstrated that coadministration of glial cell line‐derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC‐DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF‐enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>axon</subject><subject>Axons - physiology</subject><subject>Axons - ultrastructure</subject><subject>Cell Count</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Female</subject><subject>Ganglia, Spinal - physiology</subject><subject>GDNF</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - metabolism</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - pharmacology</subject><subject>Myelin Sheath - physiology</subject><subject>myelination</subject><subject>Nerve Fibers, Myelinated - physiology</subject><subject>Nerve Fibers, Myelinated - ultrastructure</subject><subject>Nerve Regeneration - drug effects</subject><subject>Nerve Regeneration - physiology</subject><subject>Neurites - physiology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Neurons - ultrastructure</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>regeneration</subject><subject>Schwann cell</subject><subject>Schwann Cells - physiology</subject><subject>Schwann Cells - transplantation</subject><subject>Sciatic Nerve - physiology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal Cord Injuries - surgery</subject><subject>Spinal Cord Injuries - therapy</subject><subject>spinal cord injury</subject><issn>0894-1491</issn><issn>1098-1136</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1vFCEUhonR2LV64w8wXGnSZCrMwMDcmDS13TauNfEjXhKGObOlsrCFGbv772WdtepNr8iB5zx5yYvQS0qOKSHl26Wz-rgkkpFHaEZJIwtKq_oxmhHZsIKyhh6gZyndEELzIJ6iA9pQQagsZ2gzf391XoC_1t5Ah_UmeO1whCV4iHqwwWPtO7zagrN-mvvgXLizfonT2u5oE2KHrb8Z4xbbhFfQWT1kWbvF62hXOl9D34MZEs7rHsYYfHqOnvTaJXixPw_Rt_Ozr6cXxeLT_PL0ZFEYzhkp6g5qLtuG07YtG6mFYSUAYYI1oJkhWrSkE6LtW9kL0TdtxSkTVMpSGFkDrw7Ru8m7HtuczIAfonZqH0wFbdX_L95eq2X4qUrJecOrLHizF8RwO0Ia1MomA85pD2FMSjAmCGEVyeTrB8laMF7Tcqc8mkATQ0oR-vs4lKhdpWpXqfpdaYZf_fuBv-i-wwzQCbizDrYPqNR8cXnyR1pMOzYNsLnf0fFHTlkJrr5fzdXnD_XHL_UFVaz6BXGovcI</recordid><startdate>20090815</startdate><enddate>20090815</enddate><creator>Zhang, Liqun</creator><creator>Ma, Zhengwen</creator><creator>Smith, George M.</creator><creator>Wen, Xuejun</creator><creator>Pressman, Yelena</creator><creator>Wood, Patrick M.</creator><creator>Xu, Xiao-Ming</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20090815</creationdate><title>GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons</title><author>Zhang, Liqun ; Ma, Zhengwen ; Smith, George M. ; Wen, Xuejun ; Pressman, Yelena ; Wood, Patrick M. ; Xu, Xiao-Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5540-6de658b951bb298a7c42ee04749ea4c0a7b0d77bfb8f77f9b3514718827c86e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>axon</topic><topic>Axons - physiology</topic><topic>Axons - ultrastructure</topic><topic>Cell Count</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Female</topic><topic>Ganglia, Spinal - physiology</topic><topic>GDNF</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - metabolism</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - pharmacology</topic><topic>Myelin Sheath - physiology</topic><topic>myelination</topic><topic>Nerve Fibers, Myelinated - physiology</topic><topic>Nerve Fibers, Myelinated - ultrastructure</topic><topic>Nerve Regeneration - drug effects</topic><topic>Nerve Regeneration - physiology</topic><topic>Neurites - physiology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Neurons - ultrastructure</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>regeneration</topic><topic>Schwann cell</topic><topic>Schwann Cells - physiology</topic><topic>Schwann Cells - transplantation</topic><topic>Sciatic Nerve - physiology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal Cord Injuries - surgery</topic><topic>Spinal Cord Injuries - therapy</topic><topic>spinal cord injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Liqun</creatorcontrib><creatorcontrib>Ma, Zhengwen</creatorcontrib><creatorcontrib>Smith, George M.</creatorcontrib><creatorcontrib>Wen, Xuejun</creatorcontrib><creatorcontrib>Pressman, Yelena</creatorcontrib><creatorcontrib>Wood, Patrick M.</creatorcontrib><creatorcontrib>Xu, Xiao-Ming</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>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Glia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Liqun</au><au>Ma, Zhengwen</au><au>Smith, George M.</au><au>Wen, Xuejun</au><au>Pressman, Yelena</au><au>Wood, Patrick M.</au><au>Xu, Xiao-Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons</atitle><jtitle>Glia</jtitle><addtitle>Glia</addtitle><date>2009-08-15</date><risdate>2009</risdate><volume>57</volume><issue>11</issue><spage>1178</spage><epage>1191</epage><pages>1178-1191</pages><issn>0894-1491</issn><eissn>1098-1136</eissn><abstract>We previously demonstrated that coadministration of glial cell line‐derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC‐DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF‐enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19170182</pmid><doi>10.1002/glia.20840</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals axon Axons - physiology Axons - ultrastructure Cell Count Cell Proliferation Cells, Cultured Coculture Techniques Female Ganglia, Spinal - physiology GDNF Glial Cell Line-Derived Neurotrophic Factor - metabolism Glial Cell Line-Derived Neurotrophic Factor - pharmacology Myelin Sheath - physiology myelination Nerve Fibers, Myelinated - physiology Nerve Fibers, Myelinated - ultrastructure Nerve Regeneration - drug effects Nerve Regeneration - physiology Neurites - physiology Neurons - drug effects Neurons - physiology Neurons - ultrastructure Random Allocation Rats Rats, Sprague-Dawley regeneration Schwann cell Schwann Cells - physiology Schwann Cells - transplantation Sciatic Nerve - physiology Spinal Cord Injuries - physiopathology Spinal Cord Injuries - surgery Spinal Cord Injuries - therapy spinal cord injury |
| title | GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons |
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