Ketogenic modulation of GABAergic neurodevelopment in C. elegans

Autores
Giunti, Sebastián; de Rosa, Maria Jose; Rayes, Diego Hernán
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
PTEN is a negative regulator of the conserved PI3K pathway. Mutations in this gene are strongly associated with neurodevelopmental disorders, epilepsy, and schizophrenia. Several reports suggest that an increase in the excitation/inhibition ratio in the brain is a hallmark of these disorders. However, it is not known whether PTEN activity can lead to this E/I imbalance. The C. elegans NM system, where both excitatory (ACh) and inhibitory (GABA) motor neurons regulate muscle activity, provides a suitable model for studying E/I balance. We found that daf-18 (C. elegans ortholog of PTEN) mutants phenotypes are typical of worms with GABAergic signaling deficits. We also found that daf-18 mutants exhibit a significantly high frequency of process defects, abnormal branching, and incomplete commissures in GABAergic neurons. These defects are observed in the earliest larval stage (L1), suggesting a neurodevelopment failure. In contrast, we did not find significant differences in the morphology of cholinergic neurons. Our genetic experiments demonstrated that the GABAergic deficit in daf-18 mutants is entirely dependent on the inactivation of the transcription factor DAF-16/FOXO3A. Interestingly, we found that all these defects are ameliorated when daf-18 mutants are exposed to the ketone body hydroxybutyrate, a FOXO3A inductor. These results may contribute to understanding PTEN-associated disorders and the mechanisms linking ketogenic diets with an improvement in these pathologies
Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXVII Congreso anual Sociedad Argentina de Neurociencias 2022
Buenos Aires
Argentina
Sociedad Argentina de Neurociencias
Materia
C. ELEGANS
KETOGENIC DIET
PTEN
NEURODEVELOPMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/229724
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Ketogenic modulation of GABAergic neurodevelopment in C. elegansGiunti, Sebastiánde Rosa, Maria JoseRayes, Diego HernánC. ELEGANSKETOGENIC DIETPTENNEURODEVELOPMENThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1PTEN is a negative regulator of the conserved PI3K pathway. Mutations in this gene are strongly associated with neurodevelopmental disorders, epilepsy, and schizophrenia. Several reports suggest that an increase in the excitation/inhibition ratio in the brain is a hallmark of these disorders. However, it is not known whether PTEN activity can lead to this E/I imbalance. The C. elegans NM system, where both excitatory (ACh) and inhibitory (GABA) motor neurons regulate muscle activity, provides a suitable model for studying E/I balance. We found that daf-18 (C. elegans ortholog of PTEN) mutants phenotypes are typical of worms with GABAergic signaling deficits. We also found that daf-18 mutants exhibit a significantly high frequency of process defects, abnormal branching, and incomplete commissures in GABAergic neurons. These defects are observed in the earliest larval stage (L1), suggesting a neurodevelopment failure. In contrast, we did not find significant differences in the morphology of cholinergic neurons. Our genetic experiments demonstrated that the GABAergic deficit in daf-18 mutants is entirely dependent on the inactivation of the transcription factor DAF-16/FOXO3A. Interestingly, we found that all these defects are ameliorated when daf-18 mutants are exposed to the ketone body hydroxybutyrate, a FOXO3A inductor. These results may contribute to understanding PTEN-associated disorders and the mechanisms linking ketogenic diets with an improvement in these pathologiesFil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaXXXVII Congreso anual Sociedad Argentina de Neurociencias 2022Buenos AiresArgentinaSociedad Argentina de NeurocienciasSociedad Argentina de Neurociencias2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/229724Ketogenic modulation of GABAergic neurodevelopment in C. elegans; XXXVII Congreso anual Sociedad Argentina de Neurociencias 2022; Buenos Aires; Argentina; 2022; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/info:eu-repo/semantics/altIdentifier/url/https://csan2022.saneurociencias.org.ar/index.php/2022/09/23/145-ketogenic-modulation-of-gabaergic-neurodevelopment-in-c-elegans/index.htmlNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:42:18Zoai:ri.conicet.gov.ar:11336/229724instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-05 10:42:19.237CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ketogenic modulation of GABAergic neurodevelopment in C. elegans
title Ketogenic modulation of GABAergic neurodevelopment in C. elegans
spellingShingle Ketogenic modulation of GABAergic neurodevelopment in C. elegans
Giunti, Sebastián
C. ELEGANS
KETOGENIC DIET
PTEN
NEURODEVELOPMENT
title_short Ketogenic modulation of GABAergic neurodevelopment in C. elegans
title_full Ketogenic modulation of GABAergic neurodevelopment in C. elegans
title_fullStr Ketogenic modulation of GABAergic neurodevelopment in C. elegans
title_full_unstemmed Ketogenic modulation of GABAergic neurodevelopment in C. elegans
title_sort Ketogenic modulation of GABAergic neurodevelopment in C. elegans
dc.creator.none.fl_str_mv Giunti, Sebastián
de Rosa, Maria Jose
Rayes, Diego Hernán
author Giunti, Sebastián
author_facet Giunti, Sebastián
de Rosa, Maria Jose
Rayes, Diego Hernán
author_role author
author2 de Rosa, Maria Jose
Rayes, Diego Hernán
author2_role author
author
dc.subject.none.fl_str_mv C. ELEGANS
KETOGENIC DIET
PTEN
NEURODEVELOPMENT
topic C. ELEGANS
KETOGENIC DIET
PTEN
NEURODEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv PTEN is a negative regulator of the conserved PI3K pathway. Mutations in this gene are strongly associated with neurodevelopmental disorders, epilepsy, and schizophrenia. Several reports suggest that an increase in the excitation/inhibition ratio in the brain is a hallmark of these disorders. However, it is not known whether PTEN activity can lead to this E/I imbalance. The C. elegans NM system, where both excitatory (ACh) and inhibitory (GABA) motor neurons regulate muscle activity, provides a suitable model for studying E/I balance. We found that daf-18 (C. elegans ortholog of PTEN) mutants phenotypes are typical of worms with GABAergic signaling deficits. We also found that daf-18 mutants exhibit a significantly high frequency of process defects, abnormal branching, and incomplete commissures in GABAergic neurons. These defects are observed in the earliest larval stage (L1), suggesting a neurodevelopment failure. In contrast, we did not find significant differences in the morphology of cholinergic neurons. Our genetic experiments demonstrated that the GABAergic deficit in daf-18 mutants is entirely dependent on the inactivation of the transcription factor DAF-16/FOXO3A. Interestingly, we found that all these defects are ameliorated when daf-18 mutants are exposed to the ketone body hydroxybutyrate, a FOXO3A inductor. These results may contribute to understanding PTEN-associated disorders and the mechanisms linking ketogenic diets with an improvement in these pathologies
Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXVII Congreso anual Sociedad Argentina de Neurociencias 2022
Buenos Aires
Argentina
Sociedad Argentina de Neurociencias
description PTEN is a negative regulator of the conserved PI3K pathway. Mutations in this gene are strongly associated with neurodevelopmental disorders, epilepsy, and schizophrenia. Several reports suggest that an increase in the excitation/inhibition ratio in the brain is a hallmark of these disorders. However, it is not known whether PTEN activity can lead to this E/I imbalance. The C. elegans NM system, where both excitatory (ACh) and inhibitory (GABA) motor neurons regulate muscle activity, provides a suitable model for studying E/I balance. We found that daf-18 (C. elegans ortholog of PTEN) mutants phenotypes are typical of worms with GABAergic signaling deficits. We also found that daf-18 mutants exhibit a significantly high frequency of process defects, abnormal branching, and incomplete commissures in GABAergic neurons. These defects are observed in the earliest larval stage (L1), suggesting a neurodevelopment failure. In contrast, we did not find significant differences in the morphology of cholinergic neurons. Our genetic experiments demonstrated that the GABAergic deficit in daf-18 mutants is entirely dependent on the inactivation of the transcription factor DAF-16/FOXO3A. Interestingly, we found that all these defects are ameliorated when daf-18 mutants are exposed to the ketone body hydroxybutyrate, a FOXO3A inductor. These results may contribute to understanding PTEN-associated disorders and the mechanisms linking ketogenic diets with an improvement in these pathologies
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/229724
Ketogenic modulation of GABAergic neurodevelopment in C. elegans; XXXVII Congreso anual Sociedad Argentina de Neurociencias 2022; Buenos Aires; Argentina; 2022; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/229724
identifier_str_mv Ketogenic modulation of GABAergic neurodevelopment in C. elegans; XXXVII Congreso anual Sociedad Argentina de Neurociencias 2022; Buenos Aires; Argentina; 2022; 1-1
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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