Effects of Long-Term Treatment with Quercetin on Cognition and Mitochondrial Function in a Mouse Model of Alzheimer’s Disease

Abstract

Amyloid-β (Aβ)-induced mitochondrial dysfunction has been recognized as a prominent, early event in Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuro-protective effects, but its preventive effects on Aβ-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two quercetin (either 20 or 40 mg kg(-1) day(-1)) groups, or an Aricept (2 mg kg(-1) day(-1)) group. After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg kg(-1) day(-1)), including lessening learning and memory deficits, reducing scattered senile plaques, and ameliorating mitochondrial dysfunction, as evidenced by restoration of mitochondrial membrane potential, reactive oxygen species and ATP levels in mitochondria isolated from the hippocampus compared to control. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated (40 mg kg(-1) day(-1)) group. These findings suggest that a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms by which quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of AD.

AltitudeOmics: The Basic Biology of Human Acclimatization to High Altitude. Addendum

“…These findings are compatible with one previous study showing partial retention of ventilatory acclimatization using noninvasive indices of oxygenation and end tidal CO 2 levels after eight days at low altitude [2,54]. The drop in [Hb] from ALT16 to POST7/21 may be due to selective destruction of the youngest circulating red cells (neocytolysis) upon return to low altitude [55][56][57][58], or potentially an increase in plasma volume [59]. Physiological Retention of Acclimatization: Acute Mountain Sickness…”

“…These changes in acid-base buffering capacity, in both the arterial and CSF compartments, would lead to a greater rise in arterial and CSF [H ϩ ] for a given rise in Pa CO 2 . In support of this notion, lowering CSF bicarbonate concentration elevates the cerebrovascular CO 2 reactivity in an anesthetized dog model (27), whereas bicarbonate infusion increases cerebral perfusion pressure in patients with posttraumatic head injury (9), elevates cerebral blood volume in preterm infants (57), and lowers ventilation in healthy exercising humans at SL (44). As such, it has been suggested that the MCAv responses to CO 2 at high altitude are linked to changes in arterial acid-base balance (16,25).…”

“…It is possible that neocytolysis, the selective destruction of a population of young red blood cells [54,55,56], may have been the mechanism of this rapid loss in Hbmass. However, the strength of the evidence for neocytolysis has recently been questioned [57]. We did not measure markers of red blood cell production or examine red blood cell age distributions during high altitude acclimatization and de-acclimatization and therefore cannot provide direct evidence in support of, or against a role for, neocytolysis.…”

Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2–ARE pathway

“…Mitochondrial samples were assayed for ATP content using the ATP dependence of the light emitting luciferase-catalyzed oxidation of luciferin. ATP concentration was calculated according to a standard curve and related to protein content [45].…”

The Transcription Factor XBP1 in Memory and Cognition: implications in Alzheimer’s Disease

“…Quercetin also displays antiamyloidogenic properties, illustrated by its ability to reduce BACE1 and Aβ levels in mice (217), prevent Aβ aggregation (221,222), promote autophagy (221,223) and bind to BACE1 catalytic core as an inhibitor (224). On the other hand, quercetin enhances the effect of neurotrophic factors such as NGF (225) and BDNF (226) to foster neuronal survival and neurite outgrowth, with tangible amelioration of memory function in animal models of AD (227)(228)(229)(230)(231) and in In parallel, XBP1 can be locally synthetized within dendrites through SPRCs and transported into the nucleus to activate transcription of BDNF, Kalirin-7 and a myriad of other genes that are crucial for the survival and plasticity of neurons. mBDNF is released at synapses and activates TrkB receptors to recruit XBP1 and Kalirin-7, which controls spinogenesis through Rho-GTPases RAC1 and PAK1, resulting in a positive activation loop.…”