Dataset Information

Tetrahydrobiopterin Improves Recognition Memory in the Triple-Transgenic Mouse Model of Alzheimer's Disease, Without Altering Amyloid-? and Tau Pathologies.

ABSTRACT:

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-? (A?) 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 3xTg-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? 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.

SUBMITTER: Fanet H

PROVIDER: S-EPMC7902975 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Tetrahydrobiopterin Improves Recognition Memory in the Triple-Transgenic Mouse Model of Alzheimer's Disease, Without Altering Amyloid-β and Tau Pathologies.

Fanet Hortense H Tournissac Marine M Leclerc Manon M Caron Vicky V Tremblay Cyntia C Vancassel Sylvie S Calon Frédéric F

Journal of Alzheimer's disease : JAD 20210101 2

<h4>Background</h4>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.<h4>Objective</h4>Here, we investigated whether BH4 peripheral administra ...[more]

PMID: 33337360

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