Author, as appears in the article.: 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
Department: Bioquímica i Biotecnologia
URV's Author/s: Bulló Bonet, Mònica / Folch Lopez, Jaume
Keywords: 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
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: monica.bullo@urv.cat jaume.folch@urv.cat
Author identifier: 0000-0002-0218-7046 0000-0002-5051-8858
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Molecular Medicine. 28 (1): 48-
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
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV