Tetrahydrobiopterin improves recognition memory in the triple-transgenic mouse model of Alzheimer’s disease, without altering amyloid-β and tau pathologies
| Autor: | Hortense Fanet, Frédéric Calon, Sylvie Vancassel, Marine Tournissac, Manon Leclerc, Cyntia Tremblay, Vicky Caron |
|---|---|
| Přispěvatelé: | Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut sur la Nutrition et les Aliments Fonctionnels [université Laval, Québec] (INAF), Université Laval [Québec] (ULaval), Faculté de médecine de l'Université Laval [Québec] (ULaval), Centre Hospitalier Université Laval [Quebec] (CHUL), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Programme d'investissements - Idex Bordeaux - LAPHIA LAPHIA ANR-10-IDEX-0302, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Male medicine.medical_specialty [SDV]Life Sciences [q-bio] Mice Transgenic tau Proteins Neuropathology Disease Nitric oxide 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Alzheimer Disease Internal medicine Medicine Memory impairment Animals 3xTg-AD mice Nootropic Agents Amyloid beta-Peptides business.industry General Neuroscience Brain Recognition Psychology General Medicine Tetrahydrobiopterin Alzheimer's disease Biopterin 3. Good health Peripheral Mice Inbred C57BL Psychiatry and Mental health Clinical Psychology 030104 developmental biology Monoamine neurotransmitter Endocrinology high-fat diet chemistry tetrahydrobiopterin (BH4) Antirheumatic Agents Female Geriatrics and Gerontology business Alzheimer’s disease 030217 neurology & neurosurgery medicine.drug Research Article |
| Zdroj: | Journal of Alzheimer's Disease Journal of Alzheimer's Disease, IOS Press, 2021, 79 (2), pp.709-727. ⟨10.3233/JAD-200637⟩ |
| ISSN: | 1387-2877 |
| Popis: | International audience; *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. |
| Databáze: | OpenAIRE |
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