Activity-dependent mechanisms of axonal growth

Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)

Detalhes bibliográficos
Autor: Mesquida Veny, Francina
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/674471
Acesso em linha:http://hdl.handle.net/10803/674471
Access Level:acceso abierto
Palavra-chave:Neurones
Neuronas
Neurons
Regeneració del sistema nerviós
Regeneración del sistema nervioso
Nervous system regeneration
Axons
Axones
Interacció cel·lular
Interacción celular
Cell interaction
Lesions medul·lars
Lesiones medulares
Spinal cord injuries
Ciències Experimentals i Matemàtiques
616.8
id ES_8aef48d88c021169c596d074e7167d03
oai_identifier_str oai:www.tdx.cat:10803/674471
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Activity-dependent mechanisms of axonal growth
title Activity-dependent mechanisms of axonal growth
spellingShingle Activity-dependent mechanisms of axonal growth
Mesquida Veny, Francina
Neurones
Neuronas
Neurons
Regeneració del sistema nerviós
Regeneración del sistema nervioso
Nervous system regeneration
Axons
Axones
Interacció cel·lular
Interacción celular
Cell interaction
Lesions medul·lars
Lesiones medulares
Spinal cord injuries
Ciències Experimentals i Matemàtiques
616.8
title_short Activity-dependent mechanisms of axonal growth
title_full Activity-dependent mechanisms of axonal growth
title_fullStr Activity-dependent mechanisms of axonal growth
title_full_unstemmed Activity-dependent mechanisms of axonal growth
title_sort Activity-dependent mechanisms of axonal growth
dc.creator.none.fl_str_mv Mesquida Veny, Francina
author Mesquida Veny, Francina
author_facet Mesquida Veny, Francina
author_role author
dc.contributor.none.fl_str_mv Hervera Abad, Arnau
Río Fernández, José Antonio del
Río Fernández, José Antonio del
Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia
dc.subject.none.fl_str_mv Neurones
Neuronas
Neurons
Regeneració del sistema nerviós
Regeneración del sistema nervioso
Nervous system regeneration
Axons
Axones
Interacció cel·lular
Interacción celular
Cell interaction
Lesions medul·lars
Lesiones medulares
Spinal cord injuries
Ciències Experimentals i Matemàtiques
616.8
topic Neurones
Neuronas
Neurons
Regeneració del sistema nerviós
Regeneración del sistema nervioso
Nervous system regeneration
Axons
Axones
Interacció cel·lular
Interacción celular
Cell interaction
Lesions medul·lars
Lesiones medulares
Spinal cord injuries
Ciències Experimentals i Matemàtiques
616.8
description Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/674471
url http://hdl.handle.net/10803/674471
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 181 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412769805107200
spelling Activity-dependent mechanisms of axonal growthMesquida Veny, FrancinaNeuronesNeuronasNeuronsRegeneració del sistema nerviósRegeneración del sistema nerviosoNervous system regenerationAxonsAxonesInteracció cel·lularInteracción celularCell interactionLesions medul·larsLesiones medularesSpinal cord injuriesCiències Experimentals i Matemàtiques616.8Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)Spinal cord injuries (SCI) are a major cause of paralysis in young adults. In this type of injuries recovery is impaired as adult central nervous system (CNS) axons fail to regenerate. This results from both a loss of intrinsic growing capacities in developmental axons when they mature, together with the presence of extrinsic factors hampering this regeneration, including a glial scar together with the production of growth-inhibitory molecules, as well as a lack of injury resolution leading to a chronic inflammation. Unfortunately, despite research efforts, current therapies for this type of injuries only lead to mild improvements and among them, activity-based therapies seem to raise above the others. Activity- based therapies try to induce recovery by increasing neuronal activity, however, a proper physiological and molecular characterization of the rationale behind their success is still missing. Neuronal activity has been described to regulate transcriptional and epigenetic mechanisms; moreover, it also alters neuronal secretion with an impact on cellular dialogues. These characteristics indicate neuronal activity may be modulating both of the CNS barriers for regeneration. During this doctoral thesis we aimed to explore the influence of neuronal activity on SCIs, hypothesizing specific neuronal activations were the principal responsible for success in activity-based therapies. Particularly, we studied the role of precise manipulations of neuronal activity, using optogenetic and chemogenetic tools, in axonal growth of stimulated neurons as well as the impact these activations could have on neuronal extrinsic signalling. Our results show that optogenetic and chemogenetic stimulations of neuronal activity enhanced growth in both regenerating and refractory to regenerate neurons. However, this growth was hampered by the inhibitory molecules present in the injured CNS and did not result in functional recovery in rodent models of SCI. Our data indicated that the growth induction in specifically stimulated neurons resulted from local adjustments rather than inducing a pro-regenerative transcriptional state, as seen by our gene expression analysis of regeneration-associated genes (RAGs). Altogether, our results suggest recovery in activity-based therapies derives from the summation of various forms of plasticity, induced by their simultaneous recruitment of several circuits. In parallel, we observed that these precise modulations of neuronal activity, while unable to alter the predominant environment after SCI, could initiate previously undescribed intricate cellular dialogues. Specifically, we found an increase in the chemokine CCL21 upon nociceptor activation which triggered the response of several cell types in the injury. In proprioceptors, this CCL21 was responsible for a growth induction after CCR7 activation, which required the MEK-ERK pathway as well as the modulation of the actin cytoskeleton. Meanwhile, the CCL21 interaction with CXCR3 in other cells effectively aborted this regeneration. All in all, our work reveals the existence of a complex plethora of synergic mechanisms, far from understood, contributing to the outcome of activity-based therapies and reinforces the need for further mechanistic studies which would allow the optimization of their success.Universitat de BarcelonaHervera Abad, ArnauRío Fernández, José Antonio delRío Fernández, José Antonio delUniversitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia202220222022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion181 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/674471TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-sa/4.0/http://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6744712026-06-14T12:46:07Z
score 15.301603

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