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Tetrahydrobiopterin improves recognition memory in the triple-transgenic mouse model of Alzheimer's disease, without altering amyloid-β and tau pathologies

dc.rights.licenseopenen_US
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorFANET, Hortense
dc.contributor.authorTOURNISSAC, Marine
dc.contributor.authorLECLERC, Manon
dc.contributor.authorCARON, Vicky
dc.contributor.authorTREMBLAY, Cyntia
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorVANCASSEL, Sylvie
dc.contributor.authorCALON, Frederic
dc.date.accessioned2021-09-21T07:11:40Z
dc.date.available2021-09-21T07:11:40Z
dc.date.issued2021-01
dc.identifier.issn1387-2877 (Print) 1875-8908 (Online)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112261
dc.description.abstractEn*Background: Alzheimer's disease (AD) is a multifactorial disease, implying that multi-target treatments may be necessary to effectively cure AD. Tetrahydrobiopterin (BH4) is an enzymatic cofactor required for the synthesis of monoamines and nitric oxide that also exerts antioxidant and anti-inflammatory effects. Despite its crucial role in the CNS, the potential of BH4 as a treatment in AD has never been scrutinized. *Objective: Here, we investigated whether BH4 peripheral administration improves cognitive symptoms and AD neuropathology in the triple-transgenic mouse model of AD (3xTg-AD), a model of age-related tau and amyloid-beta (A beta) neuropathologies associated with behavior impairment. *Methods: Non-transgenic (NonTg) and 3xTg-AD mice were subjected to a control diet (5% fat - CD) or to a high-fat diet (35% fat - HFD) from 6 to 13 months to exacerbate metabolic disorders. Then, mice received either BH4 (15 mg/kg/day, i.p.) or vehicle for ten consecutive days. *Results: This sub-chronic administration of BH4 rescued memory impairment in 13-month-old 3 xTg-AD mice, as determined using the novel object recognition test. Moreover, the HFD-induced glucose intolerance was completely reversed by the BH4 treatment in 3xTg-AD mice. However, the HFD or BH4 treatment had no significant impact on A beta and tau neuropathologies. *Conclusion: Overall, our data suggest a potential benefit from BH4 administration against AD cognitive and metabolic deficits accentuated by HFD consumption in 3xTg-AD mice, without altering classical neuropathology. Therefore, BH4 should be considered as a candidate for drug repurposing, at least in subtypes of cognitively impaired patients experiencing metabolic disorders.
dc.description.sponsorshipIdEx Bordeaux - ANR-10-IDEX-0003-02/10-IDEX-0003en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subject.en3xTg-AD mice
dc.subject.enAlzheimer's disease
dc.subject.enHigh-fat diet
dc.subject.enTetrahydrobiopterin (BH4)
dc.title.enTetrahydrobiopterin improves recognition memory in the triple-transgenic mouse model of Alzheimer's disease, without altering amyloid-β and tau pathologies
dc.typeArticle de revueen_US
dc.identifier.doi10.3233/JAD-200637en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed33337360en_US
dc.description.sponsorshipEuropeProgram Initiative d’Excellenceen_US
bordeaux.journalJournal of Alzheimer's Diseaseen_US
bordeaux.page709-727en_US
bordeaux.volume79en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue2en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut National de la Recherche Agronomiqueen_US
bordeaux.identifier.funderIDUniversité de Bordeauxen_US
bordeaux.identifier.funderIDCanadian Institutes of Health Researchen_US
bordeaux.identifier.funderIDCanada Foundation for Innovationen_US
bordeaux.identifier.funderIDFonds de Recherche du Québec - Santéen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Alzheimer's%20Disease&rft.date=2021-01&rft.volume=79&rft.issue=2&rft.spage=709-727&rft.epage=709-727&rft.eissn=1387-2877%20(Print)%201875-8908%20(Online)&rft.issn=1387-2877%20(Print)%201875-8908%20(Online)&rft.au=FANET,%20Hortense&TOURNISSAC,%20Marine&LECLERC,%20Manon&CARON,%20Vicky&TREMBLAY,%20Cyntia&rft.genre=article


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