Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have...
| Authors: | ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Submitted version |
| Publication date: | 2010 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/36363 |
| Online Access: | https://hdl.handle.net/2445/36363 |
| Access Level: | Open access |
| Keyword: | Neurones Neurobiologia Regeneració del sistema nerviós Neurons Neurobiology Nervous system regeneration |
| _version_ | 1878738410871455744 |
|---|---|
| author | Seira Oriach, Oscar |
| author2 | Gavín Marín, Rosalina Gil Fernández, Vanessa Llorens Torres, Franc Rangel Rincones, Alejandra Helena Soriano García, Eduardo Río Fernández, José Antonio del |
| author2_role | author author author author author author |
| author_browse | Gavín Marín, Rosalina Gil Fernández, Vanessa Llorens Torres, Franc Rangel Rincones, Alejandra Helena Río Fernández, José Antonio del Seira Oriach, Oscar Soriano García, Eduardo |
| author_facet | Seira Oriach, Oscar Gavín Marín, Rosalina Gil Fernández, Vanessa Llorens Torres, Franc Rangel Rincones, Alejandra Helena Soriano García, Eduardo Río Fernández, José Antonio del |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1-40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3 (GSK3) and ERK1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3 and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: i) cerebellar granule cells and ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3 inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Lastly these regenerative effects were corroborated in the lesioned EHP in NgR1 -/- mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_ae8d4defee5bc6ae0d0cb4ad564fe8a3 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/36363 |
| publishDate | 2010 |
| publishDateSort | 2010 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 Seira Oriach, Oscar Gavín Marín, Rosalina Gil Fernández, Vanessa Llorens Torres, Franc Rangel Rincones, Alejandra Helena Soriano García, Eduardo Río Fernández, José Antonio del Neurones Neurobiologia Regeneració del sistema nerviós Neurons Neurobiology Nervous system regeneration Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1-40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3 (GSK3) and ERK1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3 and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: i) cerebellar granule cells and ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3 inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Lastly these regenerative effects were corroborated in the lesioned EHP in NgR1 -/- mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections. Wiley https://hdl.handle.net/2445/36363 |
| spellingShingle | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 Seira Oriach, Oscar Neurones Neurobiologia Regeneració del sistema nerviós Neurons Neurobiology Nervous system regeneration |
| status_str | submittedVersion |
| title | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| title_full | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| title_fullStr | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| title_full_unstemmed | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| title_short | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| title_sort | Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1 |
| topic | Neurones Neurobiologia Regeneració del sistema nerviós Neurons Neurobiology Nervous system regeneration |
| topic_facet | Neurones Neurobiologia Regeneració del sistema nerviós Neurons Neurobiology Nervous system regeneration |
| url | https://hdl.handle.net/2445/36363 |