JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function

Background and aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to...

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Autores: Busquets, Oriol, Espinosa-Jiménez, Triana, Ettcheto, Miren, Olloquequi, Jordi, Bulló, Mònica, Carro, Eva, Cantero, José Luis, Casadesús, Gemma, Folch, Jaume, Verdaguer, Ester, Auladell, Carme, Camins, Antoni
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15899
Acceso en línea:http://hdl.handle.net/20.500.12105/15899
Access Level:acceso abierto
Palabra clave:Hippocampus
Mitogen-Activated Protein Kinase 8
Animals
Body Weight
Cognition
Diet, High-Fat
Insulin
Mice
Mice, Inbred C57BL
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repository_id_str
spelling JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive functionBusquets, OriolEspinosa-Jiménez, TrianaEttcheto, MirenOlloquequi, JordiBulló, MònicaCarro, EvaCantero, José LuisCasadesús, GemmaFolch, JaumeVerdaguer, EsterAuladell, CarmeCamins, AntoniHippocampusMitogen-Activated Protein Kinase 8AnimalsBody WeightCognitionDiet, High-FatInsulinMiceMice, Inbred C57BLBackground and aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. Methods: Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. Results: Our studies demonstrated that HFD in Jnk3-/- lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. Conclusions: Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.BioMed Central (BMC)Ministerio de Economía y Competitividad (España)Government of Catalonia (España)Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)20232023-04-2620222022-05-0420222022-05-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/15899reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/158992026-06-12T12:43:37Z
dc.title.none.fl_str_mv JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
title JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
spellingShingle JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
Busquets, Oriol
Hippocampus
Mitogen-Activated Protein Kinase 8
Animals
Body Weight
Cognition
Diet, High-Fat
Insulin
Mice
Mice, Inbred C57BL
title_short JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
title_full JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
title_fullStr JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
title_full_unstemmed JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
title_sort JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
dc.creator.none.fl_str_mv Busquets, Oriol
Espinosa-Jiménez, Triana
Ettcheto, Miren
Olloquequi, Jordi
Bulló, Mònica
Carro, Eva
Cantero, José Luis
Casadesús, Gemma
Folch, Jaume
Verdaguer, Ester
Auladell, Carme
Camins, Antoni
author Busquets, Oriol
author_facet Busquets, Oriol
Espinosa-Jiménez, Triana
Ettcheto, Miren
Olloquequi, Jordi
Bulló, Mònica
Carro, Eva
Cantero, José Luis
Casadesús, Gemma
Folch, Jaume
Verdaguer, Ester
Auladell, Carme
Camins, Antoni
author_role author
author2 Espinosa-Jiménez, Triana
Ettcheto, Miren
Olloquequi, Jordi
Bulló, Mònica
Carro, Eva
Cantero, José Luis
Casadesús, Gemma
Folch, Jaume
Verdaguer, Ester
Auladell, Carme
Camins, Antoni
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Government of Catalonia (España)
Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
dc.subject.none.fl_str_mv Hippocampus
Mitogen-Activated Protein Kinase 8
Animals
Body Weight
Cognition
Diet, High-Fat
Insulin
Mice
Mice, Inbred C57BL
topic Hippocampus
Mitogen-Activated Protein Kinase 8
Animals
Body Weight
Cognition
Diet, High-Fat
Insulin
Mice
Mice, Inbred C57BL
description Background and aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. Methods: Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. Results: Our studies demonstrated that HFD in Jnk3-/- lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. Conclusions: Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-05-04
2022
2022-05-04
2023
2023-04-26
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/15899
url http://hdl.handle.net/20.500.12105/15899
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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