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.
KeywordsMitochondria Brain aging Nutrition Rice bran extract NMRI mice PGC1α
AMP-activated protein kinase
Brain-derived neurotrophic factor
Cytochrome c oxidase
cAMP response element-binding protein
Dissociated brain cells
Electron transport system
Glyceraldehyde 3-phosphate dehydrogenase
High-performance liquid chromatography
Mitochondrial respiration medium 05
Mitochondrial membrane potential
Naval Medical Research Institute
Nuclear respiratory factor
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
Quantitative real-time polymerase chain reaction
Rice bran extract
Respiratory control ratio
Residual oxygen consumption
Mitochondrial transcription factor A
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.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
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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