A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice

Abstract

Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the b-amyloid (Ab) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5 % cholesterol; the high cholesterol þ low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5 % cholesterol and 2 % Oriental plum powder; and the high cholesterol þ high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5 % cholesterol and 5 % Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Ab and b-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Ab and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

“…In our experiment, despite an approximately fourfold increase in TC plasma levels, we observed no marked change in brain TC. These findings are in contrast to another study (14), which showed that cholesterol concentrations in both blood and brain were significantly higher in the HC group than in the control group. It should be noted that in that study 5% cholesterol was administered in comparison with the 2% cholesterol dose in our study.…”

“…To elucidate the effect of a high cholesterol diet on APP processing, we assayed the expression of BACE1 in the hippocampus homogenates of rats and found a significant increase in the hippocampal expression of BACE1. In support of our findings, Kuo et al have also reported a significant increase in the mRNA expression of CYP46A1, BACE1 and 24S-OHC levels in the hippocampus and brain cortex (14). In another study, Ghribi et al (36) demonstrated that feeding rabbits with 1% cholesterol for 7 months led to increased levels of BACE1.…”

“…A study by Milagre et al (11) showed that neurodegeneration leads to a change in the CYP46A1-dependent pathway. In addition, Kuo et al (14) have shown that a high cholesterol diet induces significant cognitive deficits, along with a significant increase in the mRNA expression of BACE1, Cyp46A1, and 24S-OHC levels in the hippocampus and brain cortex. 24S-OHC is a potent oxysterol with positive allosteric effects on NMDARs, which have been shown to trigger cognitive impairment and behavioral deficit in the presence of channel blockers (15).…”

Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation

“…Kuo et al reported that treating mice with a high-cholesterol diet enhanced serum and brain cholesterol concentrations, and elevated TBARS content in serum. Furthermore, highcholesterol diet-treated mice exhibited cognitive dysfunction in the Morris water maze test (27). Ettcheto et al described the relationship between hypercholesterolemia and neurodegeneration using low density lipoprotein (LDL) receptor knockout and amyloid precursor protein (APP)/presenilin (PS) 1 transgenic mice (28).…”

Polyphenols and brain health

“…Instead, recent findings have suggested that in lower amounts, typical of those attained in the diet, polyphenols may exert pharmacological activity within the cells with mechanisms that go beyond the classic antioxidant scavenging mechanisms (Williams et al, 2004;Vauzour et al, 2010). In particular, polyphenols are capable of modulating intracellular signalling cascades Vauzour et al, 2010;Kuo et al, 2015), gene expression and interactions with mitochondria (Schroeter et al, 2001;Schroeter et al, 2007;Vauzour et al, 2007b;Mandel et al, 2008). By affecting such pathways, they have the potential to induce new protein synthesis in neurons and thus an ability to induce morphological changes, which have a direct influence on memory acquisition, consolidation and storage.…”