Articles producció científica> Bioquímica i Biotecnologia

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

  • Datos identificativos

    Identificador: imarina:9262203
    Autores:
    Busquets, OriolEspinosa-Jimenez, TrianaEttcheto, MirenOlloquequi, JordiBullo, MonicaCarro, EvaCantero, Jose LuisCasadesus, GemmaFolch, JaumeVerdaguer, EsterAuladell, CarmeCamins, Antoni
    Resumen:
    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.
  • Otros:

    Autor según el artículo: Busquets, Oriol; Espinosa-Jimenez, Triana; Ettcheto, Miren; Olloquequi, Jordi; Bullo, Monica; Carro, Eva; Cantero, Jose Luis; Casadesus, Gemma; Folch, Jaume; Verdaguer, Ester; Auladell, Carme; Camins, Antoni
    Departamento: Bioquímica i Biotecnologia
    Autor/es de la URV: Bulló Bonet, Mònica / Folch Lopez, Jaume
    Palabras clave: Therapeutic target Stress Roles Protein-tyrosine-phosphatase Neurodegeneration N-terminal kinase Mitogen-activated protein kinase 8 Mice, inbred c57bl Mice Metabolism Jnk3 Jnk1 Insulin Hippocampus High-fat diet Diet, high-fat Diabetes-mellitus Dementia Cognition Body weight Animals Absence
    Resumen: 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.
    Áreas temáticas: Molecular medicine Molecular biology Medicine, research & experimental Medicina iii Medicina ii Medicina i Materiais Genetics (clinical) Genetics Engenharias iv Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Biochemistry & molecular biology
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: monica.bullo@urv.cat jaume.folch@urv.cat
    Identificador del autor: 0000-0002-0218-7046 0000-0002-5051-8858
    Fecha de alta del registro: 2024-10-12
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00471-y
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Molecular Medicine. 28 (1): 48-
    Referencia de l'ítem segons les normes APA: Busquets, Oriol; Espinosa-Jimenez, Triana; Ettcheto, Miren; Olloquequi, Jordi; Bullo, Monica; Carro, Eva; Cantero, Jose Luis; Casadesus, Gemma; Folch, (2022). JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function. Molecular Medicine, 28(1), 48-. DOI: 10.1186/s10020-022-00471-y
    DOI del artículo: 10.1186/s10020-022-00471-y
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2022
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry & Molecular Biology,Cell Biology,Genetics,Genetics (Clinical),Medicine, Research & Experimental,Molecular Biology,Molecular Medicine
    Therapeutic target
    Stress
    Roles
    Protein-tyrosine-phosphatase
    Neurodegeneration
    N-terminal kinase
    Mitogen-activated protein kinase 8
    Mice, inbred c57bl
    Mice
    Metabolism
    Jnk3
    Jnk1
    Insulin
    Hippocampus
    High-fat diet
    Diet, high-fat
    Diabetes-mellitus
    Dementia
    Cognition
    Body weight
    Animals
    Absence
    Molecular medicine
    Molecular biology
    Medicine, research & experimental
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Genetics (clinical)
    Genetics
    Engenharias iv
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Biotecnología
    Biochemistry & molecular biology
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