Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA

Abstract

Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O2) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H2O2-induced cell viability reduction in BV-2 activated cells and O2 production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Batchelor, P. E., Liberatore, G. T., Wong, J. Y., Porritt, M. J., Frerichs, F., Donnan, G. A., et al. (1999). Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Journal of Neuroscience, 19(5), 1708–1716.

    PubMed  CAS  Article  Google Scholar 

  2. Belkouch, M., Hachem, M., Elgot, A., Lo Van, A., Picq, M., Guichardant, M., et al. (2016). The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer’s disease. The Journal of Nutritional Biochemistry, 38, 1–11. https://doi.org/10.1016/j.jnutbio.2016.03.002.

    PubMed  CAS  Article  Google Scholar 

  3. Budd, S. L., Castilho, R. F., & Nicholls, D. G. (1997). Mitochondrial membrane potential and hydroethidine-monitored superoxide generation in cultured cerebellar granule cells. FEBS Letters, 415(1), 21–24.

    PubMed  CAS  Article  Google Scholar 

  4. Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., et al. (2006). Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proceedings of the National Academy of Sciences, 103(31), 11784–11789. https://doi.org/10.1073/pnas.0604681103.

    CAS  Article  Google Scholar 

  5. Calder, P. C. (2012). Mechanisms of action of (n-3) fatty acids. The Journal of Nutrition, 142(3), 592S–599S. https://doi.org/10.3945/jn.111.155259.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  6. Cao, D., Kevala, K., Kim, J., Moon, H. S., Jun, S. B., Lovinger, D., et al. (2009). Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. Journal Neurochemistry, 111(2), 510–521. https://doi.org/10.1111/j.1471-4159.2009.06335.x.

    CAS  Article  Google Scholar 

  7. Chang, C. Y., Kuan, Y. H., Li, J. R., Chen, W. Y., Ou, Y. C., Pan, H. C., et al. (2013a). Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. The Journal of Nutritional Biochemistry, 24(12), 2127–2137. https://doi.org/10.1016/j.jnutbio.2013.08.004.

    PubMed  CAS  Article  Google Scholar 

  8. Chang, C. Y., Kuan, Y. H., Li, J. R., Chen, W. Y., Ou, Y. C., Pan, H. C., et al. (2013b). Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. Journal of Nutritional Biochemistry, 24(12), 2127–2137. https://doi.org/10.1016/j.jnutbio.2013.08.004.

    PubMed  CAS  Article  Google Scholar 

  9. Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., & Peterson, P. K. (1992). Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. The Journal of Immunology, 149, 2736–2741.

    PubMed  CAS  Google Scholar 

  10. Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014). Neuroinflammation and M2 microglia: The good, the bad, and the inflamed. Journal of Neuroinflammation, 11(1), 98. https://doi.org/10.1186/1742-2094-11-98.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  11. Cobourne-Duval, M., Taka, E., Mendonca, P., Bauer, D., & Soliman, K. (2016). The antioxidant effects of thymoquinone in activated BV-2 murine microglial cells. Neurochemical Research, 41(12), 3227–3238. https://doi.org/10.1007/s11064-016-2047-1.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  12. Cole, G. M., Ma, Q. L., & Frautschy, S. A. (2009). Omega-3 fatty acids and dementia. Prostaglandins Leukot Essent Fatty Acids, 81(2–3), 213–221. https://doi.org/10.1016/j.plefa.2009.05.015.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  13. Coombes, E., Jiang, J., Xiang-Ping, C., Inoue, K., Seeds, J., Branigan, D., et al. (2011). Pathophysiologically relevant levels of hydrogen peroxide induce glutamate-independent neurodegeneration that involves activation of transient receptor potential melastatin 7 channels. Antioxidants & Redox Signaling, 14(10), 1815–1827. https://doi.org/10.1089/ars.2010.349.

    CAS  Article  Google Scholar 

  14. Desagher, S., & Martinou, J. C. (2000). Mitochondria as the central control point of apoptosis. Trends in Cell Biology, 10(9), 369–377.

    PubMed  CAS  Article  Google Scholar 

  15. Dinarello, C. A. (2010). Anti-inflammatory agents: Present and future. Cell, 140(6), 935–950. https://doi.org/10.1016/j.cell.2010.02.043.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  16. Doherty, G. H. (2011). Nitric oxide in neurodegeneration: Potential benefits of non-steroidal anti-inflammatories. Neuroscience Bulletin, 27(6), 366–382. https://doi.org/10.1007/s12264-011-1530-6.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  17. Dougherty, K. D., Dreyfus, C. F., & Black, I. B. (2000). Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiology of Disease, 7, 574–585. https://doi.org/10.1006/nbdi.2000.0318.

    PubMed  CAS  Article  Google Scholar 

  18. Ferrini, F., & De Koninck, Y. (2013). Microglia control neuronal network excitability via BDNF signalling. Neural Plasticity. https://doi.org/10.1155/2013/429815.

    PubMed  PubMed Central  Article  Google Scholar 

  19. Galland, L. (2010). Diet and inflammation. Nutrition in Clinical Practice. https://doi.org/10.1177/0884533610385703.

    PubMed  Article  Google Scholar 

  20. Ghazale, H., Ramadan, N., Mantash, S., Zibara, K., El-Sitt, S., Darwish, H., Chamaa, F., Boustany, R. M., Mondello, S., Abou-Kheir, W., Soueid, J., & Kobeissy, F. (2018). Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury. Behavioural Brain Research. https://doi.org/10.1016/j.bbr.2017.11.007.

    Article  PubMed  Google Scholar 

  21. Gibson, R. A., Neumann, M. A., Lien, E. L., Boyd, K. A., & Tu, W. C. (2013). Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins Leukotrienes and Essential Fatty Acids, 88(1), 139–146. https://doi.org/10.1016/j.plefa.2012.04.003.

    CAS  Article  Google Scholar 

  22. Glomset, J. A. (2006). Role of docosahexaenoic acid in neuronal plasma membranes. Science’s STKE. https://doi.org/10.1126/stke.3212006pe6.

    PubMed  Article  Google Scholar 

  23. Gresa-Arribas, N., Vieitez, C., Dentesano, G., Serratosa, J., Saura, J., & Sola, C. (2012). Modelling neuroinflammation in vitro: A tool to test the potential neuroprotective effect of anti-inflammatory agents. PLoS ONE, 7(9), e45227. https://doi.org/10.1371/journal.pone.0045227.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  24. Gu, F., Chauhan, V., & Chauhan, A. (2015). Glutathione redox imbalance in brain disorders. Current Opinion in Clinical Nutrition & Metabolic Care, 18(1), 89–95. https://doi.org/10.1097/MCO.0000000000000134.

    CAS  Article  Google Scholar 

  25. Hao, S., Dey, A., Yu, X., & Stranahan, A. M. (2016). Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain, Behavior, and Immunity, 51, 230–239. https://doi.org/10.1016/j.bbi.2015.08.023.

    PubMed  Article  Google Scholar 

  26. Hashimoto, M., Hossain, S., Al Mamun, A., Matsuzaki, K., & Arai, H. (2016). Docosahexaenoic acid: One molecule diverse functions. Critical Reviews in Biotechnology, 37(5), 1–19.

    Google Scholar 

  27. Hashimoto, M., Katakura, M., Tanabe, Y., Al Mamun, A., Inoue, T., Hossain, S., et al. (2015). n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats. Biochimica et Biophysica Acta (BBA): Molecular and Cell Biology of Lipids, 1851(2), 203–209. https://doi.org/10.1016/j.bbalip.2014.10.009.

    CAS  Article  Google Scholar 

  28. Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., et al. (2015). Neuroinflammation in Alzheimer’s disease. Lancet Neurology, 14(4), 388–405.

    PubMed  CAS  Article  Google Scholar 

  29. Heras-Sandoval, D., Pedraza-Chaverri, J., & Perez-Rojas, J. M. (2016). Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer’s disease. Journal of Neuroinflammation, 13(1), 61. https://doi.org/10.1186/s12974-016-0525-7.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  30. Hong, S., Lu, Y., Yang, R., Gotlinger, K. H., Petasis, N. A., & Serhan, C. N. (2007). Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms. Journal of the American Society for Mass Spectrometry, 18(1), 128–144. https://doi.org/10.1016/j.jasms.2006.09.002.

    PubMed  CAS  Article  Google Scholar 

  31. Jain, S., Banerjee, B. D., Ahmed, R. S., Arora, V. K., & Mediratta, P. K. (2013). Possible role of oxidative stress and brain derived neurotrophic factor in triazophos induced cognitive impairment in rats. Neurochemical Research, 38, 2136–2147.

    PubMed  CAS  Article  Google Scholar 

  32. Jansen, G. A., Waterham, H. R., & Wanders, R. J. (2004). Molecular basis of Refsum disease: Sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Human Mutation, 23(3), 209–218. https://doi.org/10.1002/humu.10315.

    PubMed  CAS  Article  Google Scholar 

  33. Jiang, L. H., Shi, Y., Wang, L. S., & Yang, Z. R. (2009). The influence of orally administered docosahexaenoic acid on cognitive ability in aged mice. The Journal of Nutritional Biochemistry, 20(9), 735–741. https://doi.org/10.1016/j.jnutbio.2008.07.003.

    PubMed  CAS  Article  Google Scholar 

  34. Kahlert, S., Schonfeld, P., & Reiser, G. (2005). The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes. Neurobiology of Disease, 18(1), 110–118. https://doi.org/10.1016/j.nbd.2004.08.010.

    PubMed  CAS  Article  Google Scholar 

  35. Kim, H. Y., Akbar, M., & Kim, Y. S. (2010a). Phosphatidylserine-dependent neuroprotective signalling promoted by docosahexaenoic acid. Prostaglandins Leukot Essent Fatty Acids, 82(4–6), 165–72. https://doi.org/10.1016/j.plefa.2010.02.025.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  36. Kim, H. Y., Akbar, M., & Kim, Y. S. (2010b). Phosphatidylserine-dependent neuroprotective signalling promoted by docosahexaenoic acid. Prostaglandins Leukotrienes and Essential Fatty Acids, 82(4–6), 165–172. https://doi.org/10.1016/j.plefa.2010.02.025.

    CAS  Article  Google Scholar 

  37. Kong, W., Yen, J. H., Vassiliou, E., Adhikary, S., Toscano, M., & Ganea, D. (2010). Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family. Lipids in Health and Disease, 9, 12. https://doi.org/10.1186/1476-511X-9-12.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  38. Kruska, N., & Reiser, G. (2011). Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signalling through activation of free fatty acid receptor GPR40. Neurobiology of Disease, 43(2), 465–472. https://doi.org/10.1016/j.nbd.2011.04.020.

    PubMed  CAS  Article  Google Scholar 

  39. Kuda, O. (2017). Bioactive metabolites of docosahexaenoic acid. Biochimie, 136, 12–20.

    PubMed  CAS  Article  Google Scholar 

  40. Latour, A., Grintal, B., Champeil-Potokar, G., Hennebelle, M., Lavialle, M., Dutar, P., et al. (2013). Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1. Aging Cell, 12(1), 76–84. https://doi.org/10.1111/acel.12026.

    PubMed  CAS  Article  Google Scholar 

  41. Laurén, H. B., Ruohonen, S., Kukko-Lukjanov, T. K., Virta, J. E., Grönman, M., Lopez-Picon, F. R., et al. (2013). Status epilepticus alters neurogenesis and decreases the number of GABAergic neurons in the septal dentate gyrus of 9-day-old rats at the early phase of epileptogenesis. Brain Research, 1516, 33–44. https://doi.org/10.1016/j.brainres.2013.04.028.

    PubMed  CAS  Article  Google Scholar 

  42. Lauritzen, L., Hansen, H. S., Jorgensen, M. H., & Michaelsen, K. F. (2001). The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Progress in Lipid Research, 40(1–2), 1–94. https://doi.org/10.1016/S0163-7827(00)00017-5.

    PubMed  CAS  Article  Google Scholar 

  43. Lee, T. H., Kato, H., Chen, S. T., Kogure, K., & Itoyama, Y. (2002). Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons. Neuroreport, 13(17), 2271–2275. https://doi.org/10.1097/01.wnr.0000043410.7262.

    PubMed  CAS  Article  Google Scholar 

  44. Lefkowitz, D. L., & Lefkowitz, S. S. (2008). Microglia and myeloperoxidase: A deadly partnership in neurodegenerative disease. Free Radical Biology and Medicine, 45(5), 726–731. https://doi.org/10.1016/j.freeradbiomed.2008.05.021.

    PubMed  CAS  Article  Google Scholar 

  45. Lei, B., Mace, B., Dawson, H. N., Warner, D. S., Laskowitz, D. T., & James, M. L. (2014). Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia. PLoS ONE, 9(7), e103969. https://doi.org/10.1371/journal.pone.0103969.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  46. Li, L., Wu, Y., Wang, Y., Wu, J., Song, L., Xian, W., et al. (2014). Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells. Journal of Neuroinflammation, 11, 72. https://doi.org/10.1186/1742-2094-11-72.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  47. Lian, H., Yang, L., Cole, A., Sun, L., Chiang, A. C. A., Fowler, S. W., et al. (2015). NF kappa B-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer’s disease. Neuron, 85(1), 101–115. https://doi.org/10.1016/j.neuron.2014.11.018.

    PubMed  CAS  Article  Google Scholar 

  48. Lu, Y., Zhao, L. X., Cao, D. L., & Gao, Y. J. (2013). Spinal injection of docosahexaenoic acid attenuates carrageenan-induced inflammatory pain through inhibition of microglia-mediated neuroinflammation in the spinal cord. Neuroscience, 241, 22–31. https://doi.org/10.1016/j.neuroscience.2013.03.003.

    PubMed  CAS  Article  Google Scholar 

  49. Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., et al. (2003). Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. Journal of Biological Chemistry, 278(44), 43807–43817. https://doi.org/10.1074/jbc.M305841200.

    PubMed  CAS  Article  Google Scholar 

  50. McColl, A. J., & Converse, C. A. (1995). Lipid studies in retinitis pigmentosa. Progress in Lipid Research, 34(1), 1–16.

    PubMed  CAS  Article  Google Scholar 

  51. McGahon, B. M., Martin, D. S., Horrobin, D. F., & Lynch, M. A. (1999). Age-related changes in synaptic function: Analysis of the effect of dietary supplementation with omega-3 fatty acids. Neuroscience, 94(1), 305–314.

    PubMed  CAS  Article  Google Scholar 

  52. Minghetti, L. (2004). Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. Journal of Neuropathology & Experimental Neurology, 63(9), 901–910.

    CAS  Article  Google Scholar 

  53. Moncada, S., & Bolanos, J. P. (2006). Nitric oxide, cell bioenergetics and neurodegeneration. Journal of Neurochemistry, 97(6), 1676–1689. https://doi.org/10.1111/j.1471-4159.2006.03988.x.

    PubMed  CAS  Article  Google Scholar 

  54. Okun, E., Mattson, M. P., & Arumugam, T. V. (2010). Involvement of Fc receptors in disorders of the central nervous system. Neuromolecular Medicine, 12(2), 164–178. https://doi.org/10.1007/s12017-009-8099-5.

    PubMed  CAS  Article  Google Scholar 

  55. Pereira, H., Barreira, L., Figueiredo, F., Custodio, L., Vizetto-Duarte, C., Polo, C., et al. (2012). Polyunsaturated fatty acids of marine macroalgae: Potential for nutritional and pharmaceutical applications. Marine Drugs, 10(9), 1920–1935. https://doi.org/10.3390/md10091920.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  56. Pettit, L., Vaesanyi, C., Tadros, J., & Vassiliou, E. (2013). Modulating the inflammatory properties of activated microglia with docosahexaenoic acid and aspirin. Lipids in Health and Disease, 12, 16. https://doi.org/10.1186/1476-511X-12-16.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  57. Qian, L., Gao, X., Pei, Z., Wu, X., Block, M., Wilson, B., et al. (2007). NADPH oxidase inhibitor DPI is neuroprotective at femtomolar concentrations through inhibition of microglia over-activation. Parkinsonism & Related Disorders, 13(Suppl 3), 316–320. https://doi.org/10.1016/S1353-8020(08)70023-3.

    Article  Google Scholar 

  58. Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R.,et al (2007). Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia, 55, 452–462. https://doi.org/10.1002/glia.20467.

    Article  Google Scholar 

  59. Rao, J. S., Ertley, R. N., Lee, H. J., DeMar, J. C. Jr., Arnold, J. T., Rapoport, S. I., et al. (2007). n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Molecular Psychiatry, 12(1), 36–46. https://doi.org/10.1038/sj.mp.4001888.

    PubMed  CAS  Article  Google Scholar 

  60. Reiser, G., Schonfeld, P., & Kahlert, S. (2006). Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment. International Journal of Developmental Neuroscience, 24(2–3), 113–122. https://doi.org/10.1016/j.ijdevneu.2005.11.002.

    PubMed  CAS  Article  Google Scholar 

  61. Remington, L. T., Babcock, A. A., Zehntner, S. P., & Owens, T. (2007). Microglial recruitment, activation, and proliferation in response to primary demyelination. The American Journal of Pathology, 170(5), 1713–1724. https://doi.org/10.2353/ajpath.2007.060783.

    PubMed  PubMed Central  Article  Google Scholar 

  62. Ronicke, S., Kruska, N., Kahlert, S., & Reiser, G. (2009). The influence of the branched-chain fatty acids pristanic acid and Refsum disease-associated phytanic acid on mitochondrial functions and calcium regulation of hippocampal neurons, astrocytes, and oligodendrocytes. Neurobiology of Disease, 36(2), 401–410. https://doi.org/10.1016/j.nbd.2009.08.005.

    PubMed  CAS  Article  Google Scholar 

  63. Salemme, A., Togna, A. R., Mastrofrancesco, A., Cammisotto, V., Ottaviani, M., Bianco, A., et al. (2016). Anti-inflammatory effects and antioxidant activity of dihydroasparagusic acid in lipopolysaccharide-activated microglial cells. Brain Research Bulletin, 120, 151–158. https://doi.org/10.1016/j.brainresbull.2015.11.014.

    PubMed  CAS  Article  Google Scholar 

  64. SanGiovanni, J. P., & Chew, E. Y. (2005). The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Progress in Retinal and Eye Research, 24(1), 87–138. https://doi.org/10.1016/j.preteyeres.2004.06.002.

    PubMed  CAS  Article  Google Scholar 

  65. Schonfeld, P., Kahlert, S., & Reiser, G. (2006). A study of the cytotoxicity of branched-chain phytanic acid with mitochondria and rat brain astrocytes. Experimental Gerontology, 41(7), 688 – 96. https://doi.org/10.1016/j.exger.2006.02.013.

    PubMed  CAS  Article  Google Scholar 

  66. Schonfeld, P., & Reiser, G. (2006). Rotenone-like action of the branched-chain phytanic acid induces oxidative stress in mitochondria. Journal of Biological Chemistry, 281(11), 7136–7142. https://doi.org/10.1074/jbc.M513198200.

    PubMed  CAS  Article  Google Scholar 

  67. Schonfeld, P., & Reiser, G. (2016). Brain lipotoxicity of phytanic acid and very long-chain fatty acids: Harmful cellular/mitochondrial activities in Refsum disease and x-linked adrenoleukodystrophy. Aging and Disease, 7(2), 136 – 49. https://doi.org/10.14336/AD.2015.0823.

    PubMed  PubMed Central  Article  Google Scholar 

  68. Schonfeld, P., & Struy, H. (1999). Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. FEBS Letter, 457(2), 179–183.

    CAS  Article  Google Scholar 

  69. Schonfeld, P., & Wojtczak, L. (2007). Fatty acids decrease mitochondrial generation of reactive oxygen species at the reverse electron transport but increase it at the forward transport. Biochimica et Biophysica Acta (BBA): Bioenergetics, 1767(8), 1032–1040. https://doi.org/10.1016/j.bbabio.2007.04.005.

    CAS  Article  Google Scholar 

  70. Sriram, K., Matheson, J. M., Benkovic, S. A., Miller, D. B., Luster, M. I., & O’Callaghan, J. P. (2002). Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: Implications for Parkinson’s disease. FASEB Journal, 16(11), 1474–1476. https://doi.org/10.1096/fj.02-0216fje.

    PubMed  CAS  Article  Google Scholar 

  71. Stewart, V. C., & Heales, S. J. (2003). Nitric oxide-induced mitochondrial dysfunction: Implications for neurodegeneration. Free Radical Biology and Medicine, 34(3), 287–303.

    PubMed  CAS  Article  Google Scholar 

  72. Sugasini, D., Thomas, R., Yalagala, P. C. R., Tai, L. M., & Subbaiah, P. V. (2017). Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice. Scientific Reports, 7(1), 11263. https://doi.org/10.1038/s41598-017-11766-0.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  73. Tu, W. C., Cook-Johnson, R. J., James, M. J., Muhlhausler, B. S., Stone, D. A., & Gibson, R. A. (2012). Barramundi (Lates calcarifer) desaturase with delta6/delta8 dual activities. Biotechnology Letters, 34(7), 1283–1296. https://doi.org/10.1007/s10529-012-0891-x.

    PubMed  CAS  Article  Google Scholar 

  74. Tuller, E. R., Beavers, C. T., Lou, J. R., Ihnat, M. A., Benbrook, D. M., & Ding, W. Q. (2009). Docosahexaenoic acid inhibits superoxide dismutase 1 gene transcription in human cancer cells: The involvement of peroxisome proliferator-activated receptor alpha and hypoxia-inducible factor-2 alpha signalling. Molecular Pharmacology, 76(3), 588–595. https://doi.org/10.1124/mol.109.057430.

    PubMed  CAS  Article  Google Scholar 

  75. Tyagi, E., Zhuang, Y., Agrawal, R., Ying, Z., & Gomez-Pinilla, F. (2015). Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet. Neurobiology of Disease, 73, 307–318.

    PubMed  CAS  Article  Google Scholar 

  76. Ulmann, L., Hatcher, J. P., Hughes, J. P., Chaumont, S., Green, P. J., Conquet, F., et al. (2008). Up-regulation of P2 × 4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. Journal of Neuroscience, 28(44), 11263–11268. https://doi.org/10.1523/JNEUROSCI.2308-08.2008.

    PubMed  CAS  Article  Google Scholar 

  77. Virgili, N., Espinosa-Parrilla, J. F., Mancera, P., Pastén-Zamorano, A., Gimeno-Bayon, J., Rodríguez, M. J., et al. (2011). Oral administration of the kATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis. Journal of Neuroscience, 8, 149. https://doi.org/10.1186/1742-2094-8-149.

    CAS  Article  Google Scholar 

  78. Wallstrom, P., Bjartell, A., Gullberg, B., Olsson, H., & Wirfalt, E. (2007). A prospective study on dietary fat and incidence of prostate cancer (Malmo, Sweden). Cancer Causes and Control, 18(10), 1107–1121. https://doi.org/10.1007/s10552-007-9050-4.

    PubMed  Article  Google Scholar 

  79. Wanders, R. J., Komen, J., & Ferdinandusse, S. (2011). Phytanic acid metabolism in health and disease. Biochimica et Biophysica Acta, 1811(9), 498–507. https://doi.org/10.1016/j.bbalip.2011.06.006.

    PubMed  CAS  Article  Google Scholar 

  80. Wang, H., Li, C., Wang, H., Mei, F., Liu, Z., Shen, H. Y., et al. (2013). Cuprizone-induced demyelination in mice: Age-related vulnerability and exploratory behavior deficit. Neuroscience Bulletin, 29(2), 251–259. https://doi.org/10.1007/s12264-013-1323-1.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  81. Wen, J., Ribeiro, R., & Zhang, Y. (2011). Specific PKC isoforms regulate LPS-stimulated iNOS induction in murine microglial cells. Journal of Neuroinflammation, 8, 38. https://doi.org/10.1186/1742-2094-8-38.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  82. Williams, C. M., & Burdge, G. (2006). Long-chain n-3 PUFA: Plant v. marine sources. Proceedings of the Nutrition Society, 65(1), 42–50.

    PubMed  CAS  Article  Google Scholar 

  83. Wlodarczyk, A., Holtman, I., Krueger, M., Yogev, N., Bruttger, J., Khorooshi, R., et al. (2017). A novel microglial subset plays a key role in myelinogenesis in developing brain. EMBO Journal, 36(22), 3292–3308. https://doi.org/10.15252/embj.201696056.

    PubMed  CAS  Article  Google Scholar 

  84. Wu, A., Ying, Z., & Gomez-Pinilla, F. (2004). Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. Journal of Neurotrauma, 21(10), 1457–1467. https://doi.org/10.1089/neu.2004.21.1457.

    PubMed  Article  Google Scholar 

  85. Wu, Z., Yu, J., Zhu, A., & Nakanishi, H. (2016). Nutrients, microglia aging, and brain aging. Oxidative Medicine and Cellular Longevity, 2016, 7498528. https://doi.org/10.1155/2016/7498528.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  86. Xue, B., Yang, Z., Wang, X., & Shi, H. (2012). Omega-3 polyunsaturated fatty acids antagonize macrophage inflammation via activation of AMPK/SIRT1 pathway. PLoS ONE, 7(10), e45990. https://doi.org/10.1371/journal.pone.0045990.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  87. Yan, S. D., Stern, D., Kane, M. D., Kuo, Y. M., Lampert, H. C., & Roher, A. E. (1998). RAGE-abeta interactions in the pathophysiology of Alzheimer’s disease. Restorative Neurology and Neuroscience, 12(2–3), 167–173.

    PubMed  CAS  Google Scholar 

  88. Zhu, W., Ding, Y., Kong, W., Li, T., & Chen, H. (2018) Docosahexaenoic acid (DHA) provides neuroprotection in traumatic brain injury models via activating Nrf2-ARE signalling. Inflammation. https://doi.org/10.1007/s10753-018-0765-z.

    Article  PubMed  Google Scholar 

  89. Zuniga, J., Cancino, M., Medina, F., Varela, P., Vargas, R., Tapia, G., et al. (2011). N-3 PUFA supplementation triggers PPAR-alpha activation and PPAR-alpha/NF-kappaB interaction: Anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS ONE, 6(12), e28502. https://doi.org/10.1371/journal.pone.0028502.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from “Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016” (RTC-2014-1689-1).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Beatriz Martín-Fernández.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 2227 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ruiz-Roso, M.B., Olivares-Álvaro, E., Quintela, J.C. et al. Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA. Neuromol Med 20, 328–342 (2018). https://doi.org/10.1007/s12017-018-8496-8

Download citation

Keywords

  • DHA
  • Phytanic acid
  • Microglia
  • Oxidation
  • BDNF