The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans

Autores
Giunti, Sebastián; de Rosa, Maria Jose; Rayes, Diego Hernán
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of the Akt/PKB pathway, are associated with neurodevelopmental disorders (NDDs). In recent years, ketogenic diets (KGDs) have been shown to have beneficial behavioral effects in animal models of NDDs. Ketogenic diets trigger a metabolic shift by forcing the production of ketone bodies (KBs) to generate ATP. The mechanisms underlying the beneficial effects of KGDs on NDDs are unknown. Here we used daf-18/PTEN mutants of C. elegans to gain molecular and cellular insights into the effects of KGDs on neurodevelopment. We find that these mutants are defective in exerting a complex behavior such as the escape response. These behavioral defects improve in animals cultured in the presence of KB β-hydroxybutyrate (βHB). Surprisingly, exposure to βHB at early stages is sufficient to achieve this improvement throughout adulthood, suggesting that βHB is necessary at a critical stage of development. We have also found that the effect of βHB is abolished in daf-16/FOXO mutants, revealing a key role for this transcription factor. Finally, we observed morphological defects in GABAergic motor neurons in daf-18 mutants. We are exploring whether exposure to βHB can amend these abnormalities. Given the high level of conservation of the pathways involved (PTEN/AKT/FOXO) across the animal kingdom, this work could contribute to better understand NDDs and establishing potential therapeutic options in mammals
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
XXXVI Annual Meeting (SAN2021)
Argentina
Sociedad Argentina de Investigacion en Neurociencia
Materia
C. ELEGANS
KETONIC BODIES
PTEN/DAF18
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:11336/201043
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegansGiunti, Sebastiánde Rosa, Maria JoseRayes, Diego HernánC. ELEGANSKETONIC BODIESPTEN/DAF18https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of the Akt/PKB pathway, are associated with neurodevelopmental disorders (NDDs). In recent years, ketogenic diets (KGDs) have been shown to have beneficial behavioral effects in animal models of NDDs. Ketogenic diets trigger a metabolic shift by forcing the production of ketone bodies (KBs) to generate ATP. The mechanisms underlying the beneficial effects of KGDs on NDDs are unknown. Here we used daf-18/PTEN mutants of C. elegans to gain molecular and cellular insights into the effects of KGDs on neurodevelopment. We find that these mutants are defective in exerting a complex behavior such as the escape response. These behavioral defects improve in animals cultured in the presence of KB β-hydroxybutyrate (βHB). Surprisingly, exposure to βHB at early stages is sufficient to achieve this improvement throughout adulthood, suggesting that βHB is necessary at a critical stage of development. We have also found that the effect of βHB is abolished in daf-16/FOXO mutants, revealing a key role for this transcription factor. Finally, we observed morphological defects in GABAergic motor neurons in daf-18 mutants. We are exploring whether exposure to βHB can amend these abnormalities. Given the high level of conservation of the pathways involved (PTEN/AKT/FOXO) across the animal kingdom, this work could contribute to better understand NDDs and establishing potential therapeutic options in mammalsFil: 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; ArgentinaXXXVI Annual Meeting (SAN2021)ArgentinaSociedad Argentina de Investigacion en NeurocienciaSociedad Argentina de Investigación en Neurociencias2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201043The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans; XXXVI Annual Meeting (SAN2021); Argentina; 2021; 83-83CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:23Zoai:ri.conicet.gov.ar:11336/201043instacron: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:34982025-09-03 10:10:23.683CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
title The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
spellingShingle The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
Giunti, Sebastián
C. ELEGANS
KETONIC BODIES
PTEN/DAF18
title_short The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
title_full The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
title_fullStr The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
title_full_unstemmed The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans
title_sort The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of 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
KETONIC BODIES
PTEN/DAF18
topic C. ELEGANS
KETONIC BODIES
PTEN/DAF18
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of the Akt/PKB pathway, are associated with neurodevelopmental disorders (NDDs). In recent years, ketogenic diets (KGDs) have been shown to have beneficial behavioral effects in animal models of NDDs. Ketogenic diets trigger a metabolic shift by forcing the production of ketone bodies (KBs) to generate ATP. The mechanisms underlying the beneficial effects of KGDs on NDDs are unknown. Here we used daf-18/PTEN mutants of C. elegans to gain molecular and cellular insights into the effects of KGDs on neurodevelopment. We find that these mutants are defective in exerting a complex behavior such as the escape response. These behavioral defects improve in animals cultured in the presence of KB β-hydroxybutyrate (βHB). Surprisingly, exposure to βHB at early stages is sufficient to achieve this improvement throughout adulthood, suggesting that βHB is necessary at a critical stage of development. We have also found that the effect of βHB is abolished in daf-16/FOXO mutants, revealing a key role for this transcription factor. Finally, we observed morphological defects in GABAergic motor neurons in daf-18 mutants. We are exploring whether exposure to βHB can amend these abnormalities. Given the high level of conservation of the pathways involved (PTEN/AKT/FOXO) across the animal kingdom, this work could contribute to better understand NDDs and establishing potential therapeutic options in mammals
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
XXXVI Annual Meeting (SAN2021)
Argentina
Sociedad Argentina de Investigacion en Neurociencia
description Mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of the Akt/PKB pathway, are associated with neurodevelopmental disorders (NDDs). In recent years, ketogenic diets (KGDs) have been shown to have beneficial behavioral effects in animal models of NDDs. Ketogenic diets trigger a metabolic shift by forcing the production of ketone bodies (KBs) to generate ATP. The mechanisms underlying the beneficial effects of KGDs on NDDs are unknown. Here we used daf-18/PTEN mutants of C. elegans to gain molecular and cellular insights into the effects of KGDs on neurodevelopment. We find that these mutants are defective in exerting a complex behavior such as the escape response. These behavioral defects improve in animals cultured in the presence of KB β-hydroxybutyrate (βHB). Surprisingly, exposure to βHB at early stages is sufficient to achieve this improvement throughout adulthood, suggesting that βHB is necessary at a critical stage of development. We have also found that the effect of βHB is abolished in daf-16/FOXO mutants, revealing a key role for this transcription factor. Finally, we observed morphological defects in GABAergic motor neurons in daf-18 mutants. We are exploring whether exposure to βHB can amend these abnormalities. Given the high level of conservation of the pathways involved (PTEN/AKT/FOXO) across the animal kingdom, this work could contribute to better understand NDDs and establishing potential therapeutic options in mammals
publishDate 2021
dc.date.none.fl_str_mv 2021
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/11336/201043
The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans; XXXVI Annual Meeting (SAN2021); Argentina; 2021; 83-83
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201043
identifier_str_mv The ketone body β-hydroxybutyrate (β--OH) rescues behavioral defects in DAF-18/PTEN mutants of C. elegans; XXXVI Annual Meeting (SAN2021); Argentina; 2021; 83-83
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/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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