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2010

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/36363

Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1

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http://dx.doi.org/10.1111/j.1471-4159.2010.06726.x

Abstract

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.

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Neurones, Neurobiologia, Regeneració del sistema nerviós

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Neurons, Neurobiology, Nervous system regeneration

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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SEIRA ORIACH, Oscar, et al. Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1. Journal of Neurochemistry. 2010. Vol. 113, num. 6, pags. 1644-1658. ISSN 0022-3042. [consulted: 13 of June of 2026]. Available at: https://hdl.handle.net/2445/36363

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