Bcl-2 overexpression does not promote axonal regeneration of the entorhino-hippocampal connections in vitro after axotomy

Solé, Marta Sanz; Fontana, Xavier; Gavı́n, Rosalina; Soriano, Eduardo; Rı́o, José Antonio del

doi:10.1016/j.brainres.2004.05.107

Cited by 6 publications

(2 citation statements)

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“…Thus, a dual effect of LiCl in cell survival and axon growth is likely to be responsible for these results. Indeed, a single application of LiCl after spinal cord lesion does not promote the regeneration of rubrospinal axons (Yick et al 2004), and the over-expression of Bcl-2 does not stimulate axon regeneration per se in several lesion models (Chen and Tonegawa 1998;Chierzi et al 1999;Inoue et al 2002;Sole et al 2004). In contrast, LiCl has recently been used after spinal cord lesion (Dill et al 2008), and the results contrast with those reported by Alabed and co-workers (Alabed et al 2007; Society for Neuroscience) with respect to the inhibition of GSK3b.…”

Section: Discussionmentioning

confidence: 95%

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Seira

Gavı́n

Gil

et al. 2010

Journal of Neurochemistry

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J. Neurochem. (2010) 113, 1644–1658. Abstract Lesioned axons do not regenerate in the adult mammalian CNS, owing to the over‐expression 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 3β (GSK3β) and extracellular‐related kinase (ERK) 1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3β 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 GSK3β inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Finally, these regenerative effects were corroborated in the lesioned entorhino‐hippocampal pathway 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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Section: Discussionmentioning

confidence: 95%

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Seira

Gavı́n

Gil

et al. 2010

Journal of Neurochemistry

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“…Neuronal survival or the potentiation of the intrinsic growth potential of the axon per se do not increase the potential of axon regeneration and the presence of inhibitory molecules is thought to be the main impediment to axon re-growth [21][22][23][24]. The presence of inhibitory molecules is believed to be the main impediment to *Address correspondence to this author at the Department of Cell Biology, Parc Científic de Barcelona, University of Barcelona, Josep Samitier 1-5, E-08028 Barcelona, Spain; Tel: +34-934037118; Fax: +34-934037116; E-mail: jadelrio@pcb.ub.es; jadelrio@ub.edu axonal regeneration [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Overcoming Chondroitin Sulphate Proteoglycan Inhibition of Axon Growth in the Injured Brain: Lessons from Chondroitinase ABC

Rı́o

Soriano²

2007

CPD

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The presence of numerous axon-inhibitory molecules limits the capacity of injured neurons in the adult mammalian central nervous system (CNS) to regenerate damaged axons. Among others, chondroitin sulphate proteoglycans (CSPGs) enriched in glycosaminoglycan (GAG) chains, acting intracellularly via Rho GTPase activation and cytoskeletal modification, prevent axon re-growth after injury. However, axon regeneration can be induced by modulating the extrinsic environment or the intrinsic neural response to axon extension. Among other strategies, the use of chondroitinase ABC (ChABC) to degrade GAGs and decrease CSPG-associated inhibition has been analyzed. Recent reports have extended the use of this enzyme, in combination with cell transplantation or pharmacological treatment. The steady advances made in these combinations offer promising perspectives for the development of new therapies to repair the injured nervous system.

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Organotypic Entorhino-Hippocampal Slice Cultures—A Tool to Study the Molecular and Cellular Regulation of Axonal Regeneration and Collateral Sprouting In Vitro

Turco

Deller

2007

Methods in Molecular Biology

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Organotypic slice cultures of the brain are widely used as a tool to study fundamental questions in neuroscience. In this chapter, we focus on a protocol based on organotypic slice cultures of mouse entorhinal cortex and hippocampus that can be employed to study axonal regeneration and collateral sprouting in the central nervous system in vitro. Using pharmacological as well as genetic approaches, axonal regeneration and sprouting can be influenced, and some of the molecular and cellular mechanisms involved in these processes can be identified. The protocol describes in detail (1) the generation of organotypic entorhino-hippocampal slice cultures, (2) the conditions needed for the analysis of axonal regeneration and collateral sprouting, respectively, (3) the lesioning technique, (4) tracing techniques to visualize regenerating entorhinal axons, and (5) an immunohistochemical technique to visualize sprouting fibers.

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Bcl-2 overexpression does not promote axonal regeneration of the entorhino-hippocampal connections in vitro after axotomy

Cited by 6 publications

References 35 publications

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1

Overcoming Chondroitin Sulphate Proteoglycan Inhibition of Axon Growth in the Injured Brain: Lessons from Chondroitinase ABC

Organotypic Entorhino-Hippocampal Slice Cultures—A Tool to Study the Molecular and Cellular Regulation of Axonal Regeneration and Collateral Sprouting In Vitro

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