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Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

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Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer’s disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies. To mimic the use of RBE as food additive, we have now investigated the effects of a long-term (6 months) feeding of RBE on survival, behavior and brain mitochondrial function in aged NMRI mice. RBE administration significantly increased survival and performance of aged NMRI mice in the passive avoidance and Y-maze test. Brain mitochondrial dysfunction found in aged mice was ameliorated after RBE administration. Furthermore, data from mRNA and protein expression studies revealed an up-regulation of mitochondrial proteins in RBE-fed mice, suggesting an increase in mitochondrial content which is mediated by a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-dependent mechanism. Our findings suggest that a long-term treatment with a nutraceutical containing RBE could be useful for slowing down brain aging and thereby delaying or even preventing AD.

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Alzheimer’s disease


AMP-activated protein kinase


Beta-2 microglobulin


Brain-derived neurotrophic factor


Complex I


Complex II


Complex III


Complex IV


Complex V


Cytochrome c oxidase


cAMP response element-binding protein


Citrate synthase


Dissociated brain cells


Dynamin-related protein


Electron transport system




Growth-associated protein


Glyceraldehyde 3-phosphate dehydrogenase


High-performance liquid chromatography




Mitochondrial respiration medium 05


Mitochondrial membrane potential


Naval Medical Research Institute


Nuclear respiratory factor


Optic atrophy


Oxidative phosphorylation


Parkinson’s disease


Peroxisome proliferator-activated receptor gamma coactivator 1-alpha


Phosphoglycerate kinase


Quantitative real-time polymerase chain reaction


Rice bran extract


Respiratory control ratio


Residual oxygen consumption




Sodium nitroprusside


Mitochondrial transcription factor A


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This work was funded by the German Federal Ministry for Economic Affairs and Energy (Grant No. KF2118004CS3). Authors thank Dr. Amr Helal from IT&M SA (Giza, Egypt) and Dr. Hesham El-Askary (Faculty of Pharmacy, Cairo University) for providing and characterizing the rice bran extract.

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Correspondence to Gunter P. Eckert.

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The protocol for the animal feeding study and tissue collection was approved by the local authorities for animal welfare, and all experiments were carried out according to the European Communities Council Directive (86/609/EEC) by individuals with appropriate training.

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Supplementary Fig. 10. Body weight of young and aged NMRI mice (for more information about the treatment of mice see labeling of Figure 1) over the three (young control) respectively six month (aged control, aged + RBE) study period; mean without SEM (EPS 75 kb)

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Hagl, S., Asseburg, H., Heinrich, M. et al. Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice. Neuromol Med 18, 347–363 (2016).

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