Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 17-07-2015
| Autor: | |
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | español |
| OAI Identifier: | oai:repositorio.uam.es:10486/674471 |
| Acceso en línea: | http://hdl.handle.net/10486/674471 |
| Access Level: | acceso abierto |
| Palabra clave: | Proteína Tau - Tesis doctorales Proteína tau - Tesis doctorales Enfermedades neurodegenerativas - Tesis doctorales Biología y Biomedicina / Biología |
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Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| title |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| spellingShingle |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta Pallas Bazarra, Noemí Proteína Tau - Tesis doctorales Proteína tau - Tesis doctorales Enfermedades neurodegenerativas - Tesis doctorales Biología y Biomedicina / Biología |
| title_short |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| title_full |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| title_fullStr |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| title_full_unstemmed |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| title_sort |
Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adulta |
| dc.creator.none.fl_str_mv |
Pallas Bazarra, Noemí |
| author |
Pallas Bazarra, Noemí |
| author_facet |
Pallas Bazarra, Noemí |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Llorens Martín, María Victoria Hernández Pérez, Félix Garrido Jurado, Juan José Departamento de Biología Molecular Facultad de Ciencias Centro de Biología Molecular Severo Ochoa (CBM) |
| dc.subject.none.fl_str_mv |
Proteína Tau - Tesis doctorales Proteína tau - Tesis doctorales Enfermedades neurodegenerativas - Tesis doctorales Biología y Biomedicina / Biología |
| topic |
Proteína Tau - Tesis doctorales Proteína tau - Tesis doctorales Enfermedades neurodegenerativas - Tesis doctorales Biología y Biomedicina / Biología |
| description |
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 17-07-2015 |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-07-17 |
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doctoral thesis http://purl.org/coar/resource_type/c_db06 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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http://hdl.handle.net/10486/674471 |
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http://hdl.handle.net/10486/674471 |
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Español spa |
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Español |
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spa |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Estudio del papel de la proteína Tau en la modulación de la neurogénesis hipocampal adultaPallas Bazarra, NoemíProteína Tau - Tesis doctoralesProteína tau - Tesis doctoralesEnfermedades neurodegenerativas - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 17-07-2015Alterations in tau protein metabolism are found in a subset of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer´s disease. As several tauopathies are accompanied by memory deficits, and adult hippocampal neurogenesis is crucial for learning and memory, tau protein might be involved in this process. In fact, Tau isoforms with three microtubule‐binding domains (Tau3R) and high phosphorylation levels are found in neurons during embryonic development and also in murine adult newborn neurons, but not in mature neurons in the adult brain. Therefore, the aim of this work was to study the role of Tau protein on adult hippocampal neurogenesis. Besides, since adult neurogenesis is regulated by different environmental factors, we were aimed to investigate the role of Tau in the regulation of adult neurogenesis that either pro‐ or anti‐ neurogenic stimuli exert. We have studied Tau knockout mice (Dawson et al., 2001) to analyze the generation and maturation of newborn neurons in the dentate gyrus. We have used three different approaches to study the effect of lacking tau protein on this region: thymidine analogs (in order to study cell survival at different time points), PSD95‐GFP retrovirus infection (to analyze the morphology and connectivity of newborn neurons), and specific markers (to analyze the different stages of newborn cells maturation). These methodologies were combined with the use of several behavioral tests aimed to analyze the effect of lacking tau protein on hippocampal‐dependent memory (Novel Object Location Preference test) and mood‐related behaviors (Elevated Plus Maze and Porsolt tests). As a pro‐neurogenic stimulus we have used environmental enrichment, and as an anti‐neurogenic stimulus we have used the acute stressor induced by the Porsolt test. The results showed, first, that lacking Tau protein has no effects on adult hippocampal neurogenesis rate under basal conditions. However, it impairs dendritic development and results in postsynaptic density (PSD) alterations. Nevertheless, these alterations are not accompanied by impairments of behavioral pattern separation tasks nor by the appearance of depression‐like behavior, although an increase in anxiety‐like behavior was detected in these mice. On the other hand, lacking Tau protein weakened the pro‐neurogenic effects of environmental enrichment on adult hippocampal neurogenesis. It resulted in an attenuated increase in adult neurogenesis rate. Besides, nor dendritogenesis nor synaptic adaptations to the higher activity demand took place on mature newborn neurons in absence of Tau as they did in the wild type mice. Finally, lacking Tau protein exerted neuroprotective effects on adult hippocampal neurogenesis after acute stress. It partially protected immature newborn neurons against Porsolt test induced cell death. Moreover, after newborn neurons completed their maturation, the lack of Tau protein was still neuroprotective with regard to stress induced damage in their dendrites and synaptic connections. Summarizing, lack of Tau protein does not seem to produce marked alterations in the basal rate of adult hippocampal neurogenesis, although Tau seems to be involved in newborn neuron maturation. In addition, it plays a crucial role in the modulation of adult hippocampal neurogenesis exerted by either positive or negative stimuli.Llorens Martín, María VictoriaHernández Pérez, FélixGarrido Jurado, Juan JoséDepartamento de Biología MolecularFacultad de CienciasCentro de Biología Molecular Severo Ochoa (CBM)20152015-07-17doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/674471reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6744712026-06-23T12:46:27Z |
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15,300724 |