| dc.rights.license | open | en_US |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | MEDINA-VERA, Dina | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | ZAMBRANA-INFANTES, Emma N. | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | LOPEZ-GAMBERO, Antonio J. | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | VERHEUL-CAMPOS, Julia | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | SANTÍN, Luis J. | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | BAIXERAS, Elena | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | SUAREZ, Juan | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | PAVON, Francisco J. | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | ROSELL-VALLE, Cristina | |
| hal.structure.identifier | Universidad de Málaga [Málaga] = University of Málaga [Málaga] | |
| dc.contributor.author | RODRIGUEZ DE FONSECA, Fernando | |
| dc.date.accessioned | 2024-03-26T13:56:14Z | |
| dc.date.available | 2024-03-26T13:56:14Z | |
| dc.date.issued | 2023-10-15 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/188987 | |
| dc.description.abstractEn | The amyloid cascade hypothesis is widely accepted as an explanation for the neuropathological changes in Alzheimer's disease (AD). However, the role of amyloid-beta (Aβ) as the sole cause of these changes is being questioned. Using the 5xFAD mouse model of AD, we investigated various factors contributing to neuropathology, including genetic load (heterozygous (HTZ) versus homozygous (HZ) condition), behavioural phenotype, neuropathology markers, metabolic physiology, and gut microbiota composition at early (5 months of age) and late (12 months of age) stages of disease onset, and considering both sexes. At 5 months of age, both HTZ and HZ mice exhibited hippocampal alterations associated with Aβ accumulation, leading to increased neuroinflammation and disrupted PI3K-Akt pathway. However, only HZ mice showed cognitive impairment in the Y-maze and Morris water maze tests, worsening with age. Dysregulation of both insulin and insulin secretion-regulating GIP peptide were observed at 5 months of age, disappearing later. Circulating levels of metabolic-regulating hormones, such as Ghrelin and resisting helped to differentiates HTZ mice from HZ mice. Differences between HTZ and HZ mice were also observed in gut microbiota composition, disrupted intestinal barrier proteins, and increased proinflammatory products in the intestine. These findings suggest that cognitive impairment in 5xFAD mice may not solely result from Aβ aggregation. Other factors, including altered PI3K-Akt signalling, disrupted insulin-linked metabolic pathways, and changes in gut microbiota, contribute to disease progression. Targeting Aβ deposition alone may not suffice. Understanding AD pathogenesis and its multiple contributing factors is vital for effective therapies. © 2023 The Authors | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | Akt pathway; Cognitive impairment | |
| dc.subject.en | Insulin resistance | |
| dc.subject.en | Microbiota | |
| dc.subject.en | Neuroinflammation | |
| dc.subject.en | Hippocampus | |
| dc.title.en | Transcending the amyloid-beta dominance paradigm in Alzheimer's disease: An exploration of behavioural, metabolic, and gut microbiota phenotypes in 5xFAD mice | |
| dc.title.alternative | Neurobiol Dis | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.nbd.2023.106295 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 37717663 | en_US |
| dc.description.sponsorshipEurope | European Regional Development Fund | en_US |
| dc.description.sponsorshipEurope | Defining a Roadmap for Cooperative Health research between the EU and Latin America-Caribbean countries: a Policy Oriented Approach | en_US |
| bordeaux.journal | Neurobiology of Disease | en_US |
| bordeaux.volume | 187 | en_US |
| bordeaux.hal.laboratories | Neurocentre Magendie - U1215 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | Physiopathologie de l'équilibre énergétique et obésité | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | H2020 European Research Council | en_US |
| bordeaux.identifier.funderID | Instituto de Salud Carlos III | en_US |
| hal.identifier | hal-04521779 | |
| hal.version | 1 | |
| hal.date.transferred | 2024-03-26T13:56:18Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| dc.rights.cc | CC BY-NC-ND | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Neurobiology%20of%20Disease&rft.date=2023-10-15&rft.volume=187&rft.au=MEDINA-VERA,%20Dina&ZAMBRANA-INFANTES,%20Emma%20N.&LOPEZ-GAMBERO,%20Antonio%20J.&VERHEUL-CAMPOS,%20Julia&SANT%C3%8DN,%20Luis%20J.&rft.genre=article | |
