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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
- Source :
- Journal of Alzheimer's Disease, Journal of Alzheimer's Disease, IOS Press, 2021, 79 (2), pp.709-727. ⟨10.3233/JAD-200637⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 13872877
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease, Journal of Alzheimer's Disease, IOS Press, 2021, 79 (2), pp.709-727. ⟨10.3233/JAD-200637⟩
- Accession number :
- edsair.doi.dedup.....1fead495d91f37530b23e51b15f06687