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Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer ’ s disease

View Article: PubMed Central - PubMed

ABSTRACT

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II), containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

No MeSH data available.


Related in: MedlinePlus

Nutra II increased exploratory behavior as assessed by elevated plus maze task - Diagrams show representative tracings of exploratory behavior in WT and 5XFAD mice treated with Nutra II or left untreated in the elevated plus maze task. All mice showed similar durations in open arms and closed arms.
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fig0025: Nutra II increased exploratory behavior as assessed by elevated plus maze task - Diagrams show representative tracings of exploratory behavior in WT and 5XFAD mice treated with Nutra II or left untreated in the elevated plus maze task. All mice showed similar durations in open arms and closed arms.

Mentions: In addition, 5XFAD mice exhibited reduced locomotor and exploratory activity, as evidenced by lower total distance traveled, average speed and rearing frequency in a novel environment of the open field task (Fig. 4a). Likewise, 5XFAD mice exhibited lower total distance traveled, average speed as well as total, open and closed arms entries in the elevated plus maze task (Fig. 4c, d). Notably, this hypoactivity was reversed by Nutra II treatment. No significant differences were observed in the time spent in open and closed arms of the EPM test (Fig. 5), as well as the time spent in the central and peripheral zones of the open field task (Fig. 4b), of 5XFAD compared with WT mice, indicating no change in anxiety level.


Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer ’ s disease
Nutra II increased exploratory behavior as assessed by elevated plus maze task - Diagrams show representative tracings of exploratory behavior in WT and 5XFAD mice treated with Nutra II or left untreated in the elevated plus maze task. All mice showed similar durations in open arms and closed arms.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384415&req=5

fig0025: Nutra II increased exploratory behavior as assessed by elevated plus maze task - Diagrams show representative tracings of exploratory behavior in WT and 5XFAD mice treated with Nutra II or left untreated in the elevated plus maze task. All mice showed similar durations in open arms and closed arms.
Mentions: In addition, 5XFAD mice exhibited reduced locomotor and exploratory activity, as evidenced by lower total distance traveled, average speed and rearing frequency in a novel environment of the open field task (Fig. 4a). Likewise, 5XFAD mice exhibited lower total distance traveled, average speed as well as total, open and closed arms entries in the elevated plus maze task (Fig. 4c, d). Notably, this hypoactivity was reversed by Nutra II treatment. No significant differences were observed in the time spent in open and closed arms of the EPM test (Fig. 5), as well as the time spent in the central and peripheral zones of the open field task (Fig. 4b), of 5XFAD compared with WT mice, indicating no change in anxiety level.

View Article: PubMed Central - PubMed

ABSTRACT

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II), containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

No MeSH data available.


Related in: MedlinePlus