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

Abstract

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.

Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice

“…Monitoring the following aging process, 18-month-old mice had a significantly reduced alternation rate and number of alternations compared to young control animals, indicating a reduced spatial learning memory and mobility in 18-month-old NMRI mice (Figures 1(a) and 1(b)) which is in agreement with previous studies [29,36]. In comparison, other studies already showed a significantly decreased performance in the Ymaze test in middle-aged mice [43,49].…”

“…Effect of Aging on Cognitive Performance. Spatial learning memory and locomotor activity were determined using the Y-maze spontaneous alternation test in 3-, 6-, 12-, and 18month-old mice [29,35,36]. Mice, aged 6 or 12 months, showed slightly but not significantly decreased changes in alternation rates compared to young controls during a five-minute testing phase (Figure 1(a)).…”

“…Therefore, we measured the development of the energy metabolism and mRNA expression of genes involved in mitochondrial biogenesis, antioxidant capacity, and synaptic plasticity in the brain as well as the cognitive performance every six months in the same cohort of female NMRI mice. Female NMRI mice are a well-described outbred mouse model for the physiological, "normal" aging process which reflects a high variability of the genome [27][28][29]. This model has been described as most suitable for studies on physiological aging compared to inbred or genetically modified mouse models with accelerated aging or reduced lifespans [30,31].…”

Rice Bran as a Functional Food: An Overview of the Conversion of Rice Bran into a Superfood/Functional Food

“…Long-term supplementation has a positive impact on survival, cognition and brain mitochondrial function, which may delay Alzheimer's disease [64]. Rice bran supplements can also be used as ergogenic supplements by body builders and athletes [65] and they may mitigate menopausal symptoms such as hot flashes, as well as bone loss in older women who suffer from osteoporosis [66].…”

“…Rice bran HRV induced diarrhea prevention in gnotobiotic pigs 10% ↑ Intestinal IFN-γ and total IgA levels [63] γ-Oryzanol Brain aging in NMRI mice 4 g/kg diet for 6 months ↑ Mitochondrial proteins [64] γ-Oryzanol Human health growth 500 mg/day ↑ Muscular strength (bench press and squat) and vertical jump power [65] γ-Oryzanol Postmenoposal osteoporosis in rats 0.3% crystalized oryzanol ↑ Estrogen, Bone mineral [66] HRV, human rota virus; IFN-γ, interferon gamma; IgA, immunoglobulin A. …”