Spinal Axon Regeneration Induced by Elevation of Cyclic AMP
Myelin inhibitors, including MAG, are major impediments to CNS regeneration. However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2002-06, Vol.34 (6), p.895-903 |
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| container_title | Neuron (Cambridge, Mass.) |
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| creator | Qiu, Jin Cai, Dongming Dai, Haining McAtee, Marietta Hoffman, Paul N. Bregman, Barbara S. Filbin, Marie T. |
| description | Myelin inhibitors, including MAG, are major impediments to CNS regeneration. However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is PKA dependent. By 1 week post-lesion, DRG-cAMP returns to control, but growth on MAG/myelin improves and is now PKA independent. Inhibiting PKA in vivo blocks the post-lesion growth on MAG/myelin at 1 day and attenuates it at 1 week. Alone, injection of db-cAMP into the DRG mimics completely a conditioning lesion as DRGs grow on MAG/myelin, initially, in a PKA-dependent manner that becomes PKA independent. Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury. |
| doi_str_mv | 10.1016/S0896-6273(02)00730-4 |
| format | Article |
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However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is PKA dependent. By 1 week post-lesion, DRG-cAMP returns to control, but growth on MAG/myelin improves and is now PKA independent. Inhibiting PKA in vivo blocks the post-lesion growth on MAG/myelin at 1 day and attenuates it at 1 week. Alone, injection of db-cAMP into the DRG mimics completely a conditioning lesion as DRGs grow on MAG/myelin, initially, in a PKA-dependent manner that becomes PKA independent. Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/S0896-6273(02)00730-4</identifier><identifier>PMID: 12086638</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Axons - drug effects ; Axons - enzymology ; Axons - physiology ; Bucladesine - pharmacology ; Cyclic AMP - antagonists & inhibitors ; Cyclic AMP - biosynthesis ; Cyclic AMP - physiology ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Female ; Ganglia, Spinal - drug effects ; Ganglia, Spinal - physiology ; Kinases ; Medical research ; Nerve Regeneration - drug effects ; Nerve Regeneration - physiology ; Rats ; Rats, Sprague-Dawley ; Rodents ; Spinal cord</subject><ispartof>Neuron (Cambridge, Mass.), 2002-06, Vol.34 (6), p.895-903</ispartof><rights>2002 Cell Press</rights><rights>Copyright Elsevier Limited Jun 13, 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-d522d3f37c0cba4b5e7abd23bb73b62ea53484e3d673a32d38efb9610e9361403</citedby><cites>FETCH-LOGICAL-c519t-d522d3f37c0cba4b5e7abd23bb73b62ea53484e3d673a32d38efb9610e9361403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627302007304$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12086638$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Jin</creatorcontrib><creatorcontrib>Cai, Dongming</creatorcontrib><creatorcontrib>Dai, Haining</creatorcontrib><creatorcontrib>McAtee, Marietta</creatorcontrib><creatorcontrib>Hoffman, Paul N.</creatorcontrib><creatorcontrib>Bregman, Barbara S.</creatorcontrib><creatorcontrib>Filbin, Marie T.</creatorcontrib><title>Spinal Axon Regeneration Induced by Elevation of Cyclic AMP</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Myelin inhibitors, including MAG, are major impediments to CNS regeneration. However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is PKA dependent. By 1 week post-lesion, DRG-cAMP returns to control, but growth on MAG/myelin improves and is now PKA independent. Inhibiting PKA in vivo blocks the post-lesion growth on MAG/myelin at 1 day and attenuates it at 1 week. Alone, injection of db-cAMP into the DRG mimics completely a conditioning lesion as DRGs grow on MAG/myelin, initially, in a PKA-dependent manner that becomes PKA independent. Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury.</description><subject>Animals</subject><subject>Axons - drug effects</subject><subject>Axons - enzymology</subject><subject>Axons - physiology</subject><subject>Bucladesine - pharmacology</subject><subject>Cyclic AMP - antagonists & inhibitors</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Cyclic AMP - physiology</subject><subject>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Female</subject><subject>Ganglia, Spinal - drug effects</subject><subject>Ganglia, Spinal - physiology</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Nerve Regeneration - drug effects</subject><subject>Nerve Regeneration - physiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Spinal cord</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1rFDEUhkNR2m31JygDgrQXoyffE7yQZWlroWJp9TokmTOSMjuzTXaK---b7S4K3vQqnPDkPeR5CXlH4RMFqj7fQWNUrZjmp8DOADSHWhyQGQWja0GNeUVmf5EjcpzzPQAV0tBDckQZNErxZka-3K3i4Ppq_mccqlv8jQMmt45luBraKWBb-U113uPj7nLsqsUm9DFU8-83b8jrzvUZ3-7PE_Lr4vzn4lt9_ePyajG_roOkZl23krGWd1wHCN4JL1E73zLuveZeMXSSi0Ygb5Xmjhe0wc4bRQENV1QAPyEfd7mrND5MmNd2GXPAvncDjlO2mjay_PJlkDaCU6lEAT_8B96PUyoeCiOBa8WZaQold1RIY84JO7tKcenSxlKw2xLscwl2a9gCs88l2G36-3365JfY_nu1t16ArzsAi7XHiMnmEHEotmPCsLbtGF9Y8QTOpJOs</recordid><startdate>20020613</startdate><enddate>20020613</enddate><creator>Qiu, Jin</creator><creator>Cai, Dongming</creator><creator>Dai, Haining</creator><creator>McAtee, Marietta</creator><creator>Hoffman, Paul N.</creator><creator>Bregman, Barbara S.</creator><creator>Filbin, Marie T.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020613</creationdate><title>Spinal Axon Regeneration Induced by Elevation of Cyclic AMP</title><author>Qiu, Jin ; 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| subjects | Animals Axons - drug effects Axons - enzymology Axons - physiology Bucladesine - pharmacology Cyclic AMP - antagonists & inhibitors Cyclic AMP - biosynthesis Cyclic AMP - physiology Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - metabolism Female Ganglia, Spinal - drug effects Ganglia, Spinal - physiology Kinases Medical research Nerve Regeneration - drug effects Nerve Regeneration - physiology Rats Rats, Sprague-Dawley Rodents Spinal cord |
| title | Spinal Axon Regeneration Induced by Elevation of Cyclic AMP |
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