Cognitive-Enhancing Effects of a Polyphenols-Rich Extract from Fruits without Changes in Neuropathology in an Animal Model of Alzheimer’s Disease

Dal-Pan, Alexandre; Dudonné, Stéphanie; Bourassa, Philippe; Bourdoulous, Morgane; Tremblay, Cyntia; Desjardins, Yves; Calon, Frédéric

doi:10.3233/jad-160281

Cited by 51 publications

(35 citation statements)

References 91 publications

(146 reference statements)

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“…Their neuroprotective potential has been shown in both oxidative stress- [8,9] and Aβ-induced-induced neuronal death models [10]. Evidence also supports the beneficial and neuromodulatory effects of flavonoid-rich blueberry and grape extracts, particularly in connection with age-related cognitive decline and Alzheimer's disease [11,12].…”

Section: Introductionmentioning

confidence: 86%

Inhibition of PP2A by hesperetin may contribute to Akt and ERK1/2 activation status in cortical neurons

Vauzour

Corsini

Müller

et al. 2018

Archives of Biochemistry and Biophysics

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Flavonoids and their metabolites are well reported to modulate the activation/phosphorylation of various cellular kinases, such as ERK1/2 and JNK, although the mechanism by which they do so is unclear. In this study, we investigated the impact of flavanones on the activation of PI3K/Akt and ERK1/2 and determine whether this is mediated, in part, by the inhibition of phosphatases. Primary cortical neurons were exposed to physiological concentrations of hesperetin and the phosphorylation status of the kinases PI3K/Akt and ERK1/2 and the phosphatases PP2A and PTEN were assessed by immunoblotting after 30 min. Exposure to 100-300 nM hesperetin led to significant increases in the phosphorylation of ERK1/2 and Akt and significant decreases in PP2A levels and enzyme activity. Using in silico docking, hesperetin was found to fit into the active site of PP2A interacting within the hydrophobic cage of the catalytic unit. These data suggest a potential mechanism by which flavanones may lead to increased activation of ERK1/2 and Akt, commonly observed in cell models. Their interaction with and inhibition of cellular phosphatases counteract normal physiological regulation of signaling pathway activation thus facilitating and/or maintaining the activation status of ERK1/2 and Akt, important regulators of brain functions.

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Section: Introductionmentioning

confidence: 86%

Inhibition of PP2A by hesperetin may contribute to Akt and ERK1/2 activation status in cortical neurons

Vauzour

Corsini

Müller

et al. 2018

Archives of Biochemistry and Biophysics

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“…Locomotor activity was assessed with the open field test (Dal-Pan et al, 2016). Mice were placed in a 40 cm x 40 cm x 40 cm translucent Plexiglas box for an hour.…”

Section: Behavioral Testsmentioning

confidence: 99%

Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model

Tournissac

Vrabic

et al. 2020

Preprint

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Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3-adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.Here, we show that β3AR agonist administration (CL-316,243, 1 mg/kg/day i.p., from 15 to 16 months of age) decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old).Locomotion, anxiety and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.

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“…Long term green tea catechin administration (0.05-0.1% w/v) also improved spatial learning and memory in senescence prone mice, by decreasing Ab 1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus (Li et al, 2009b). However, a recent investigation reported a cognitive-enhancing effect of a polyphenol-rich without changes in either Ab or Tau pathologies, therefore suggesting that polyphenols-rich extracts may prevent memory impairment associated with age-related diseases, without significant effects on classical AD neuropathology (Dal-Pan et al, 2017). Further work is therefore required to fully apraise whether polyphenols have efficacy in individuals affected by dementia.…”

Section: Effects Of Polyphenols On Age-related Cognitive Decline and mentioning

confidence: 93%

Polyphenols and brain health

Vauzour

2017

OCL

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-Accumulating evidence suggests that diet and lifestyle can play an important role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. A growing number of dietary intervention studies in humans and animals and in particular those using polyphenol-rich diets have been proposed to exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning, and cognitive functions. These effects appear to be underpinned by two common processes. First, they are capable of interactions with critical protein and lipid kinase signalling cascades in the brain, leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Second, they induce beneficial effects on the vascular system, leading to changes in cerebrovascular blood flow capable of causing enhance vascularisation and neurogenesis, two events important in the maintenance of cognitive performances. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols might have the potential to prevent the progression of neurodegenerative pathologies.

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Cognitive-Enhancing Effects of a Polyphenols-Rich Extract from Fruits without Changes in Neuropathology in an Animal Model of Alzheimer’s Disease

Cited by 51 publications

References 91 publications

Inhibition of PP2A by hesperetin may contribute to Akt and ERK1/2 activation status in cortical neurons

Inhibition of PP2A by hesperetin may contribute to Akt and ERK1/2 activation status in cortical neurons

Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model

Polyphenols and brain health

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