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01-09-2016 | Original Paper

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

Authors: Stephanie Hagl, Heike Asseburg, Martina Heinrich, Nadine Sus, Eva-Maria Blumrich, Ralf Dringen, Jan Frank, Gunter P. Eckert

Published in: NeuroMolecular Medicine | Issue 3/2016

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.

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Afshordel, S., Hagl, S., Werner, D., Rohner, N., Kogel, D., Bazan, N. G., et al. (2015). Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging—Impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins Leukotrienes and Essential Fatty Acids, 92C, 23–31.CrossRef

Barnard, N. D., Bush, A. I., Ceccarelli, A., Cooper, J., de Jager, Celeste A, & Erickson, K. I., et al. (2014). Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease. Neurobiology of Aging, 35S2, S74–S78.

Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., et al. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444(7117), 337–342.CrossRefPubMed

Bayram, B., Nikolai, S., Huebbe, P., Ozcelik, B., Grimm, S., Grune, T., et al. (2013). Biomarkers of oxidative stress, antioxidant defence and inflammation are altered in the senescence-accelerated mouse prone 8. AGE, 35(4), 1205–1217.CrossRefPubMed

Bhullar, K. S., & Hubbard, B. P. (2015). Lifespan and healthspan extension by resveratrol. Biochimica et Biophysica Acta, 1852(6), 1209–1218.CrossRefPubMed

Canto, C., & Auwerx, J. (2009). PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current Opinion in Lipidology, 20(2), 98–105.CrossRefPubMedPubMedCentral

Chistiakov, D. A., Sobenin, I. A., Revin, V. V., Orekhov, A. N., & Bobryshev, Y. V. (2014). Mitochondrial aging and age-related dysfunction of mitochondria. BioMed Research International, 2014, 238463.PubMedPubMedCentral

Dringen, R., Kussmaul, L., & Hamprecht, B. (1998). Detoxification of exogenous hydrogen peroxide and organic hydroperoxides by cultured astroglial cells assessed by microtiter plate assay. Brain Research Protocols, 2(3), 223–228.CrossRefPubMed

Eckert, G. P., Renner, K., Eckert, S. H., Eckmann, J., Hagl, S., Abdel-Kader, R. M., et al. (2012). Mitochondrial dysfunction-a pharmacological target in Alzheimer’s disease. Molecular Neurobiology, 46(1), 136–150.CrossRefPubMed

Fernandez-Marcos, P. J., & Auwerx, J. (2011). Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. American Journal of Clinical Nutrition, 93(4), 884S–900S.CrossRefPubMedPubMedCentral

Frick, K. M., & Fernandez, S. M. (2003). Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice. Neurobiology of Aging, 24(4), 615–626.CrossRefPubMed

Grasselli, G., & Strata, P. (2013). Structural plasticity of climbing fibers and the growth-associated protein GAP-43. Frontiers in Neural Circuits, 7, 25.CrossRefPubMedPubMedCentral

Grebenstein, N., & Frank, J. (2012). Rapid baseline-separation of all eight tocopherols and tocotrienols by reversed-phase liquid-chromatography with a solid-core pentafluorophenyl column and their sensitive quantification in plasma and liver. Journal of Chromatography, 1243, 39–46.CrossRefPubMed

Grimm, A., Friedland, K., & Eckert, A. (2015). Mitochondrial dysfunction: The missing link between aging and sporadic Alzheimer’s disease. Biogerontology,. doi:10.1007/s10522-015-9618-4.PubMed

Hagl, S., Berressem, D., Bruns, B., Sus, N., Frank, J., & Eckert, G. P. (2015) Beneficial effects of ethanolic and hexanic rice bran extract on mitochondrial function in PC12 cells and the search for bioactive components. Molecules (Basel, Switzerland) 20(9), 16524–16539

Hagl, S., Berressem, D., Grewal, R., Sus, N., Frank, J., & Eckert, G. P. (2016). Rice bran extract improves mitochondrial dysfunction in brains of aged NMRI mice. Nutritional Neuroscience, 19(1), 1–10.CrossRefPubMed

Hagl, S., Grewal, R., Ciobanu, I., Helal, A., Khayyal, M. T., Muller, W. E., et al. (2015b). Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer’s disease. Journal of Alzheimer’s Disease, 43(3), 927–938.PubMed

Hagl, S., Kocher, A., Schiborr, C., Eckert, S. H., Ciobanu, I., Birringer, M., et al. (2013). Rice bran extract protects from mitochondrial dysfunction in guinea pig brains. Pharmacological Research: The Official Journal of the Italian Pharmacological Society, 76, 17–27.CrossRef

Hohnholt, M. C., & Dringen, R. (2014). Short time exposure to hydrogen peroxide induces sustained glutathione export from cultured neurons. Free Radical Biology and Medicine, 70, 33–44.CrossRefPubMed

Howes, M.-J. R., & Perry, E. (2011). The role of phytochemicals in the treatment and prevention of dementia. Drugs and Aging, 28(6), 439–468.CrossRefPubMed

Kann, O. (2015). The interneuron energy hypothesis: Implications for brain disease. Neurobiology of Diseases,. doi:10.1016/j.nbd.2015.08.005.

Kann, O., Papageorgiou, I. E., & Draguhn, A. (2014). Highly energized inhibitory interneurons are a central element for information processing in cortical networks. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 34(8), 1270–1282.CrossRef

Kim, H. G., & Oh, M. S. (2012). Nutraceuticals and prevention of neurodegeneration herbal medicines for the prevention and treatment of Alzheimer’s disease. Current Pharmaceutical Design,. doi:10.2174/138161212798919002.PubMedCentral

Kitani, K., Osawa, T., & Yokozawa, T. (2007). The effects of tetrahydrocurcumin and green tea polyphenol on the survival of male C57BL/6 mice. Biogerontology, 8(5), 567–573.CrossRefPubMed

Lagouge, M., & Larsson, N.-G. (2013). The role of mitochondrial DNA mutations and free radicals in disease and ageing. Journal of Internal Medicine, 273(6), 529–543.CrossRefPubMedPubMedCentral

Larsen, S., Nielsen, J., Hansen, C. N., Nielsen, L. B., Wibrand, F., Stride, N., et al. (2012). Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. The Journal of Physiology, 590(14), 3349–3360.CrossRefPubMedPubMedCentral

Leal, G., Afonso, P. M., Salazar, I. L., & Duarte, C. B. (2015). Regulation of hippocampal synaptic plasticity by BDNF. Brain Research, 1621, 82–101.CrossRefPubMed

Leuner, K., Hauptmann, S., Abdel-Kader, R., Scherping, I., Keil, U., Strosznajder, J. B., et al. (2007). Mitochondrial dysfunction: The first domino in brain aging and Alzheimer’s disease? Antioxidants & Redox Signaling, 9(10), 1659–1675.CrossRef

Linard, A., Macaire, J.-P., & Christon, R. (2001). Phospholipid hydroperoxide glutathione peroxidase activity and vitamin E level in the liver microsomal membrane: Effects of age and dietary alpha-linolenic acid deficiency. The Journal of Nutritional Biochemistry, 12(8), 481–491.CrossRefPubMed

Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. The Journal of biological chemistry, 193(1), 265–275.PubMed

Mamiya, T., Asanuma, T., Kise, M., Ito, Y., Mizukuchi, A., Aoto, H., et al. (2004). Effects of pre-germinated brown rice on beta-amyloid protein-induced learning and memory deficits in mice. Biological & Pharmaceutical Bulletin, 27(7), 1041–1045.CrossRef

Marlatt, M. W., Potter, M. C., Lucassen, P. J., & van Praag, H. (2012). Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Developmental Neurobiology, 72(6), 943–952.CrossRefPubMedPubMedCentral

Mattson, M. P., Gleichmann, M., & Cheng, A. (2008). Mitochondria in neuroplasticity and neurological disorders. Neuron, 60(5), 748–766.CrossRefPubMedPubMedCentral

Mattson, M. P., Maudsley, S., & Martin, B. (2004). BDNF and 5-HT: A dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends in Neurosciences, 27(10), 589–594.CrossRefPubMed

Müller, W., Eckert, A., Kurz, C., Eckert, G., & Leuner, K. (2010). Mitochondrial dysfunction: Common final pathway in brain aging and alzheimer’s disease—therapeutic aspects. Molecular Neurobiology, 41, 159–171.CrossRefPubMed

Navarro, A., Bandez, M. J., Lopez-Cepero, J. M., Gomez, C., & Boveris, A. (2011). High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging. AJP: Regulatory, Integrative and Comparative Physiology, 300(4), R827.

Navarro, A., & Boveris, A. (2010). Brain mitochondrial dysfunction in aging, neurodegeneration, and Parkinson’s disease. Frontiers in Aging Neuroscience, 2. doi:10.3389/fnagi.2010.00034.

Navarro, A., Gomez, C., Sanchez-Pino, M.-J., Gonzalez, H., Bandez, M. J., Boveris, A. D., et al. (2005). Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. American Journal of Physiology, 289(5), R1392–R1399.PubMed

Navarro, A., Sanchez Del Pino, M. J., Gomez, C., Peralta, J. L., & Boveris, A. (2002). Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. American Journal of Physiology, 282(4), R985–R992.PubMed

Pannangrong, W., Wattanathorn, J., Muchimapura, S., Tiamkao, S., & Tong-un, T. (2011). Purple rice berry is neuroprotective and enhances cognition in a rat model of alzheimer’s disease. Journal of Medicinal Food, 14(7–8), 688–694.CrossRefPubMed

Park, S.-Y. (2010). Potential therapeutic agents against Alzheimer’s disease from natural sources. Archives of Pharmacal Research, 33(10), 1589–1609.CrossRefPubMed

Patterson, S. L. (2015). Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1beta, BDNF and synaptic plasticity. Neuropharmacology, 96(Pt A), 11–18

Petters, C., & Dringen, R. (2014). Comparison of primary and secondary rat astrocyte cultures regarding glucose and glutathione metabolism and the accumulation of iron oxide nanoparticles. Neurochemical Research, 39(1), 46–58.CrossRefPubMed

Picard, M., & McEwen, B. S. (2014). Mitochondria impact brain function and cognition. Proceedings of the National Academy of Sciences of the United States of America, 111(1), 7–8.CrossRefPubMed

Rabøl, R., Larsen, S., Højberg, P. M. V., Almdal, T., Boushel, R., Haugaard, S. B., et al. (2010). Regional anatomic differences in skeletal muscle mitochondrial respiration in type 2 diabetes and obesity. Journal of Clinical Endocrinology and Metabolism, 95(2), 857–863.CrossRefPubMed

Reagan-Shaw, S., Nihal, M., & Ahmad, N. (2008). Dose translation from animal to human studies revisited. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 22(3), 659–661.CrossRef

Schaffer, S., Asseburg, H., Kuntz, S., Muller, W. E., & Eckert, G. P. (2012). Effects of polyphenols on brain ageing and Alzheimer’s disease: Focus on mitochondria. Molecular Neurobiology, 46(1), 161–178.CrossRefPubMed

Schindowski, K., Leutner, S., Kressmann, S., Eckert, A., & Muller, W. E. (2001). Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761). Journal of Neural Transmission (Vienna, Austria: 1996), 108(8–9), 969–978.

Schmoll, H., Ramboiu, S., Platt, D., Herndon, J. G., Kessler, C., & Popa-Wagner, A. (2005). Age influences the expression of GAP-43 in the rat hippocampus following seizure. Gerontology, 51(4), 215–224.CrossRefPubMed

Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, Judy C. Y., Aris, J. P., & Leeuwenburgh, C. (2010). New insights into the role of mitochondria in aging: Mitochondrial dynamics and more. Journal of Cell Science, 123(Pt 15), 2533–2542.CrossRefPubMedPubMedCentral

Shiga, T., Nakamura, T. J., Komine, C., Goto, Y., Mizoguchi, Y., Yoshida, M., et al. (2016). A single neonatal injection of ethinyl estradiol impairs passive avoidance learning and reduces expression of estrogen receptor alpha in the hippocampus and cortex of adult female rats. PLoS ONE, 11(1), e0146136.CrossRefPubMedPubMedCentral

Sunagawa, T., Shimizu, T., Kanda, T., Tagashira, M., Sami, M., & Shirasawa, T. (2011). Procyanidins from apples (Malus pumila Mill.) extend the lifespan of Caenorhabditis elegans. Planta Medica, 77(2), 122–127.CrossRefPubMed

Tarsa, L., & Goda, Y. (2002). Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America, 99(2), 1012–1016.CrossRefPubMedPubMedCentral

Tulpule, K., Hohnholt, M., Hirrlingerm J., & Dringen, R. (2014) Primary cultures of astrocytes and neurons as model systems to study the metabolism and metabolite export from brain cells. In Hirrlinger, J., Waagepetersen, H. S. (Eds.), Brain energy metabolism, Vol. 90 (pp. 45–72). New York: Springer.

Wilson, M. A., Shukitt-Hale, B., Kalt, W., Ingram, D. K., Joseph, J. A., & Wolkow, C. A. (2006). Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell, 5(1), 59–68.CrossRefPubMedPubMedCentral

Wolf, A., Bauer, B., Abner, E. L., Ashkenazy-Frolinger, T., Hartz, & Anika, M. S. (2016). A comprehensive behavioral test battery to assess learning and memory in 129S6/Tg2576 mice. PLoS ONE, 11(1), e0147733.CrossRefPubMedPubMedCentral

Title: Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice
Authors: Stephanie Hagl
Heike Asseburg
Martina Heinrich
Nadine Sus
Eva-Maria Blumrich
Ralf Dringen
Jan Frank
Gunter P. Eckert
Publication date: 01-09-2016
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 3/2016
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-016-8420-z

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Springer Medicine

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

Abstract

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Abstract

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