Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones
Schizophrenia is a devastating disease characterized by positive, negative and cognitive symptoms including impaired cognition, altered perception and affected behavior. Genes and environment are two factors with strong incidence for the development of schizophrenia but besides intensive research, i...
Guardado en:
Autor principal: | |
---|---|
Otros Autores: | |
Formato: | Tesis doctoral acceptedVersion |
Lenguaje: | Español |
Publicado: |
Facultad de Farmacia y Bioquímica
2017
|
Materias: | |
Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_3147 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3147.dir/3147.PDF |
Aporte de: |
id |
I28-R145-HWA_3147 |
---|---|
record_format |
dspace |
spelling |
I28-R145-HWA_31472020-07-16 Schizophrenia is a devastating disease characterized by positive, negative and cognitive symptoms including impaired cognition, altered perception and affected behavior. Genes and environment are two factors with strong incidence for the development of schizophrenia but besides intensive research, its etiology is still unknown. The main prescripted treatment is the administration of antipsychotics, dopamine D2 receptor (DRD2) blockers, which mainly relieve the positive symptoms, without an effective treatment for cognitive and negative symptoms. It was recently proposed that a hyperactive ventral hippocampus (vHipp) drive an increase in dopamine release from dopaminergic neurons and may cause schizophrenia. Increasing evidence suggests that cognitive impairment might be due to abnormal function of the inhibitory GABAergic neurons, particularly parvalbumin interneurons (PVI).\nIt is a major challenge to develop reliable animal models to study psychiatric diseases as schizophrenia. In the present work, a conditional mutant mouse line was generated, where dopamine D2 receptor was specifically deleted from parvalbumin interneurons. This conditional mutant mouse line exhibited cellular, molecular, physiological and behavioral defects reminiscent to schizophrenia. Pharmacologic experiments reveal that a functional DRD2 is essential in PVI for antipsychotic effectiveness.\nThe mouse line generated in the present work may be a new animal model to study schizophrenia. Fil: Tomasella, María Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Hotch, Christian Facultad de Farmacia y Bioquímica Gelman, Diego M. Tomasella, María Eugenia 2017-12-20 La esquizofrenia es un síndrome complejo del neurodesarrollo, afectado por factores genéticos y ambientales, y caracterizado por una colección heterogénea de síntomas.\nPara el diagnóstico de pacientes con esquizofrenia no existen aún hoy métodos de diagnósticos confiables. El tratamiento farmacológico por excelencia prescripto hoy en día son los antipsicóticos, que se unen y bloquean al receptor de dopamina D2.\nSe han relacionado a las disrupciones del sistema dopaminérgico con desordenes psiquiátricos como la esquizofrenia. Se postula que existe un sistema dopaminérgico hiper responsivo con la presencia de un hipocampo hiperactivo. Esto podría resultar por un funcionamiento anormal de las interneuronas GABAérgicas inhibitorias, particularmente las de parvalbúmina.\nConstituye un desafío construir modelos animales que permitan estudiar enfermedades psiquiátricas con etiología aún desconocida como la esquizofrenia. En este trabajo, se generó un modelo animal de ratón en donde se delecionó selectivamente el DRD2 de las interneuronas de PV (IPV), observándose características reminiscentes a la esquizofrenia. La misma exhibió alteraciones a nivel celular, molecular, fisiológico y de comportamiento, presentando fenotipos que son observados en pacientes con esta enfermedad. Además, los experimentos farmacológicos indicaron la importancia del DRD2 en las IPV para la efectividad de algunos antipsicóticos.\nLa línea de ratón generado en el presente trabajo pretende constituirse en un nuevo modelo animal para poder estudiar la esquizofrenia en un camino hacia comprender su etiología. application/pdf Taira, Carlos Belforte, Juan Sánche Bruni, Sergio Receptor D2 Balance Comportamiento spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_3147 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3147.dir/3147.PDF |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-145 |
collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
language |
Español |
orig_language_str_mv |
spa |
topic |
Receptor D2 Balance Comportamiento Ciencias de la vida |
spellingShingle |
Receptor D2 Balance Comportamiento Ciencias de la vida Tomasella, María Eugenia Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
topic_facet |
Receptor D2 Balance Comportamiento Ciencias de la vida |
description |
Schizophrenia is a devastating disease characterized by positive, negative and cognitive symptoms including impaired cognition, altered perception and affected behavior. Genes and environment are two factors with strong incidence for the development of schizophrenia but besides intensive research, its etiology is still unknown. The main prescripted treatment is the administration of antipsychotics, dopamine D2 receptor (DRD2) blockers, which mainly relieve the positive symptoms, without an effective treatment for cognitive and negative symptoms. It was recently proposed that a hyperactive ventral hippocampus (vHipp) drive an increase in dopamine release from dopaminergic neurons and may cause schizophrenia. Increasing evidence suggests that cognitive impairment might be due to abnormal function of the inhibitory GABAergic neurons, particularly parvalbumin interneurons (PVI).\nIt is a major challenge to develop reliable animal models to study psychiatric diseases as schizophrenia. In the present work, a conditional mutant mouse line was generated, where dopamine D2 receptor was specifically deleted from parvalbumin interneurons. This conditional mutant mouse line exhibited cellular, molecular, physiological and behavioral defects reminiscent to schizophrenia. Pharmacologic experiments reveal that a functional DRD2 is essential in PVI for antipsychotic effectiveness.\nThe mouse line generated in the present work may be a new animal model to study schizophrenia. |
author2 |
Hotch, Christian |
author_facet |
Hotch, Christian Tomasella, María Eugenia |
format |
Tesis doctoral Tesis doctoral acceptedVersion |
author |
Tomasella, María Eugenia |
author_sort |
Tomasella, María Eugenia |
title |
Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
title_short |
Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
title_full |
Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
title_fullStr |
Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
title_full_unstemmed |
Deleción selectiva del receptor dopaminérgico D2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
title_sort |
deleción selectiva del receptor dopaminérgico d2 : estudio de la alteración del balance inhibitorio-excitatorio en el comportamiento de ratones |
publisher |
Facultad de Farmacia y Bioquímica |
publishDate |
2017 |
url |
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_3147 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3147.dir/3147.PDF |
work_keys_str_mv |
AT tomasellamariaeugenia delecionselectivadelreceptordopaminergicod2estudiodelaalteraciondelbalanceinhibitorioexcitatorioenelcomportamientoderatones |
_version_ |
1766017528863129600 |