Titre :

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model

Auteur(s) :

Leboucher, Antoine [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Ahmed, Tariq [Auteur]
Caron, Emilie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Tailleux, Anne [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Raison, Sylvie [Auteur]
Institut des Neurosciences Cellulaires et Intégratives [INCI]
Joly-Amado, Aurélie [Auteur]
Marciniak, Elodie [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Carvalho, Kevin [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Hamdane, Malika [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Bantubungi, Kadiombo [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Lancel, Steve [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Eddarkaoui, Sabiha [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Caillierez, Raphaëlle [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Vallez, Emmanuelle [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Vieau, didier [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Balschun, Detlef [Auteur]
Buee, Luc [Auteur correspondant]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Blum, David [Auteur correspondant]
Excellence Laboratory LabEx DISTALZ
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]

Titre de la revue :

Neurobiology of Disease

Pagination :

14-22

Éditeur :

Elsevier

Date de publication :

2019-05

ISSN :

0969-9961

Mot(s)-clé(s) en anglais :

Alzheimer's disease
Insulin resistance
Metabolism
THY-Tau22
Tau
Transgenic mice

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]

Résumé en anglais : [en]

Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal ...
Lire la suite >Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Thus, in AD, brain insulin resistance affects both cognitive and metabolic changes described in these patients. While a role of Aβ oligomers and APOE4 towards the development of brain insulin resistance emerged, contribution of Tau pathology has been largely overlooked. Our recent data demonstrated that one of the physiological function of Tau is to sustain brain insulin signaling. We postulated that under pathological conditions, hyper-phosphorylated/aggregated Tau is likely to lose this function and to favor the development of brain insulin resistance. This hypothesis was substantiated by observations from patient brains with pure Tauopathies. To address the potential link between Tau pathology and brain insulin resistance, we have evaluated the brain response to insulin in a transgenic mouse model of AD-like Tau pathology (THY-Tau22). Using electrophysiological and biochemical evaluations, we surprisingly observed that, at a time when Tau pathology and cognitive deficits are overt and obvious, the hippocampus of THY-Tau22 mice exhibits enhanced response to insulin. In addition, we demonstrated that the ability of i.c.v. insulin to promote body weight loss is enhanced in THY-Tau22 mice. In line with this, THY-Tau22 mice exhibited a lower body weight gain, hypoleptinemia and hypoinsulinemia and finally a metabolic resistance to high-fat diet. The present data highlight that the brain of transgenic Tau mice exhibit enhanced brain response to insulin. Whether these observations are ascribed to the development of Tau pathology, and therefore relevant to human Tauopathies, or unexpectedly results from the Tau transgene overexpression is debatable and discussed.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime
Transfert différentiel intercellulaire des assemblages de Tau
Récepteurs A2A et Tauopathie
Contribution des astrocytes aux troubles cognitifs induits par la protéine Tau neuronale dans la maladie d'Alzheimer

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL