Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats

  • Milena Carvalho-Silva
  • Lara M. Gomes
  • Maria L. Gomes
  • Bruna K. Ferreira
  • Patricia F. Schuck
  • Gustavo C. Ferreira
  • Felipe Dal-Pizzol
  • Jade de Oliveira
  • Giselli Scaini
  • Emilio L. StreckEmail author
Original Article


Deficiency of hepatic enzyme tyrosine aminotransferase characterizes the innate error of autosomal recessive disease Tyrosinemia Type II. Patients may develop neurological and developmental difficulties due to high levels of the amino acid tyrosine in the body. Mechanisms underlying the neurological dysfunction in patients are poorly known. Importantly, Tyrosinemia patients have deficient Omega-3 fatty acids (n-3 PUFA). Here, we investigated the possible neuroprotective effect of the treatment with n-3 PUFA in the alterations caused by chronic administration of L-tyrosine on important parameters of energetic metabolism and oxidative stress in the hippocampus, striatum and cerebral cortex of developing rats. Chronic administration of L-tyrosine causes a decrease in the citrate synthase (CS) activity in the hippocampus and cerebral cortex, as well as in the succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) activities, and an increase in the α-ketoglutarate dehydrogenase activity in the hippocampus. Moreover, in the striatum, L-tyrosine administration caused a decrease in the activities of CS, SDH, creatine kinase, and complexes I, II-III and IV of the mitochondrial respiratory chain. We also observed that the high levels of L-tyrosine are related to oxidative stress in the brain. Notably, supplementation of n-3 PUFA prevented the majority of the modifications caused by the chronic administration of L-tyrosine in the cerebral enzyme activities, as well as ameliorated the oxidative stress in the brain regions of rats. These results indicate a possible neuroprotective and antioxidant role for n-3 PUFA and may represent a new therapeutic approach and potential adjuvant therapy to Tyrosinemia Type II individuals.


Tyrosinemia type II L-tyrosine Omega-3 fatty acids Mitochondrial energy metabolism Oxidative stress 



This research was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC).


  1. Atamna H, Frey WH (2007) Mechanisms of mitochondrial dysfunction and deficiency in Alzheimer’s disease. Mitochondrion 7:297–310. Google Scholar
  2. Avramovic N, Dragutinovic V, Krstic D, Colovic MB, Trbovic A, de Luka S, Milovanovic I, Popovic T (2012) The effects of omega 3 fatty acid supplementation on brain tissue oxidative status in aged wistar rats. Hippokratia 16(3):241245Google Scholar
  3. Barbosa PR, Cardoso MR, Daufenbach JF, Gonçalves CL, Machado RA, Roza CA, Scaini G, Rezin GT, Schuck PF, Dal-Pizzol F, Streck EL (2010) Inhibition of mitochondrial respiratory chain in the brain of rats after renal ischemia is prevented by Nacetylcysteine and deferoxamine. Metab Brain Dis 25:219–225. Google Scholar
  4. Bongiovanni R, Yamamoto BK, Simpson C, Jaskiw GE (2003) Pharmacokinetics of systemically administered tyrosine: a comparison of serum, brain tissue and in vivo microdialysate levels in the rat. J Neurochem 87:310–317. Google Scholar
  5. Cancelier K, Gomes LM, Carvalho-Silva M, Teixeira LJ, Rebelo J, Mota IT, Arent CO, Mariot E, Kist LW, Bogo MR, Quevedo J, Scaini G, Streck EL (2016) Omega-3 fatty acids and mood stabilizers alter behavioural and energy metabolism parameters in animals subjected to an animal model of mania induced by fenproporex. Mol Neurobiol 54(6):3935–3947. Google Scholar
  6. Carvalho-Silva M, Gomes LM, Scaini G, Rebelo J, Damiani AP, Pereira M, Andrade VM, Gava FF, Valvassori SS, Schuck PF, Ferreira GC, Streck EL (2017) Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II. Metab Brain Dis 32(4):1043–1050. Google Scholar
  7. Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316. Google Scholar
  8. Cheatham CL, Colombo J, Carlson SE (2006) n-3 fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations. Am J Clin Nutr 83(6):1458S–1466S. Google Scholar
  9. Chepelev NL, Bennitz JD, Wright JS, Smith JC, Willmore WG (2009) Oxidative modification of citrate synthase by peroxyl radicals and protection with novel antioxidants. J Enzyme Inhib Med Chem 24(6):1319–1331. Google Scholar
  10. Chung WL, Chen JJ, Su HM (2008) Fish oil supplementation of control and (n-3) fatty acid-deficient male rats enhances reference and working memory performance and increases brain regional docosahexaenoic acid levels. J Nutr 138(6):1165–1171. Google Scholar
  11. Cutuli D, Pagani M, Caporali P, Galbusera A, Laricchiuta D, Foti F, Neri C, Spalletta G, Caltagirone C, Petrosini L, Gozzi A (2016) Effects of Omega-3 fatty acid supplementation on cognitive functions and neural substrates: a voxel-based morphometry study in aged mice. Front Aging Neurosci 8:38. Google Scholar
  12. De Andrade RB, Gemelli T, Rojas DB, Bonorino NF, Costa BM, Funchal C, Dutra-Filho CS, Wannmacher CM (2011a) Creatine and pyruvate prevent the alterations caused by tyrosine on parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex of Wistar rats. Mol Neurobiol 51(3):1184–1194. Google Scholar
  13. De Andrade RB, Gemelli T, Rojas DB, Funchal C, Dutra-Filho CS, Wannmacher CM (2011b) Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats. Metab Brain Dis 26:221–227. Google Scholar
  14. De Andrade RB, Gemelli T, Rojas DB, Funchal C, Dutra-Filho CS, Wannmacher CM (2012) Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats. Mol Cell Biochem 364:253–261. Google Scholar
  15. De Prá SDT, Ferreira GK, Carvalho-Silva M, Vieira SV, Scaini S, Leffa D, Fagundes G, Bristot B, Borges G, Ferreira GC, Schuck PF, Andrade VM, Streck EL (2014) L-tyrosine induces DNA damage in brain and blood of rats. Neurochem Res 39:202–207. Google Scholar
  16. Decker MJ, Jones K, Keating GL, Damato EG, Darrah R (2016) Maternal dietary supplementation with omega-3 polyunsaturated fatty acids confers neuroprotection to the newborn against hypoxia-induced dopamine dysfunction. Sleep Sci 9(2):94–99. Google Scholar
  17. Dercksen M, Kulik W, Mienie LJ, Reinecke CJ, Wanders RJ, Duran M (2016) Polyunsaturated fatty acid status in treated isovaleric acidemia patients. Eur J Clin Nutr 70(10):1123–1126. Google Scholar
  18. El-Ansary AK, Al-Daihan SK, El-Gezeery AR (2011) On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups. Lipids Health Dis 10:142. Google Scholar
  19. Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421Google Scholar
  20. Fernie AR, Carrari F, Sweetlove LJ (2004) Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol 7(3):254–261. Google Scholar
  21. Ferreira GK, Carvalho-Silva M, Gonçalves CL, Vieira JS, Scaini G, Ghedim FV, Deroza PF, Zugno AI, Pereira TC, Oliveira GM, Kist LW, Bogo MR, Schuck PF, Ferreira GC, Streck EL (2012) L-tyrosine administration increases acetylcholinesterase activity in rats. Neurochem Int 61(8):1370–1374. Google Scholar
  22. Ferreira GK, Jeremias IC, Scaini G, Carvalho-Silva M, Gomes LM, Furlanetto CB, Morais MOS, Schuck PF, Ferreira GC, Streck EL (2013a) Effect of acute and chronic administration of L-tyrosine on nerve growth factor levels in rat brain. Neurochem Res 38:1742–1746. Google Scholar
  23. Ferreira GK, Scaini G, Carvalho-Silva M, Gomes LM, Borges LS, Vieira JS, Constantino LS, Ferreira GC, Schuck PF, Streck EL (2013b) Effect of L-tyrosine in vitro and in vivo on energy metabolism parameters in brain and liver of young rats. Neurotox Res 23:327–335. Google Scholar
  24. Ferreira GK, Scaini G, Jeremias IC, Carvalho-Silva M, Gonçalves CL, Pereira TC, Oliveira GM, Kist LW, Bogo MR, Schuck PF, Ferreira GC, Streck EL (2014) An evaluation of the effects of acute and chronic L-tyrosine administration on BDNF levels and BDNF mRNA expression in the rat brain. Mol Neurobiol 49(2):734–740. Google Scholar
  25. Ferreira GK, Carvalho-Silva M, Gomes LM, Scaini G, Teixeira LJ, Mota IT, Schuck PF, Ferreira GC, Streck EL (2015) The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility. Metab Brain Dis 30(1):215–221. Google Scholar
  26. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–26. Google Scholar
  27. Garcia-Cazorla A, Quadros EV, Nascimento A, Garcia-Silva MT, Briones P, Montoya J, Ormazábal A, Artuch R, Sequeira JM, Blau N, Arenas J, Pineda M, Ramaekers VT (2008) Mitochondrial diseases associated with cerebral folate deficiency. Neurology 70(16):1360–1362. Google Scholar
  28. Gil-Campos M, Sanjurjo Crespo P (2012) Omega 3 fatty acids and inborn errors of metabolism. Br J Nutr 107(2):S129–S136. Google Scholar
  29. Godwin A, Prabhu HR (2006) Lipid peroxidation of fish oils. Indian J Clin 21:202–204. Google Scholar
  30. Gokay S, Kendirci M, Ustkoyuncu PS, Kardas F, Bayram AK, Por H, Poyrazoğlu HG (2016) Tyrosinemia type II: novel mutations in TAT in a boy with unusual presentation. Pediatr Int 58(10):1069–1072. Google Scholar
  31. Goldsmith LA (1983) Tyrosinemia and related disorders. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5tn edn. McGraw-Hill, New York, p 287Google Scholar
  32. Gomes LM, Carvalho-Silva M, Teixeira LJ, Rebelo J, Mota IT, Bilesimo R, Michels M, Arent CO, Mariot E, Dal-Pizzol F, Scaini G, Quevedo J, Streck EL (2017) Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration. Metab Brain Dis 32(2):519–528. Google Scholar
  33. Gomes LM, Scaini G, Carvalho-Silva M, Gomes ML, Malgarin F, Kist LW, Bogo MR, Rico EP, Zugno AI, Deroza PFP, Réus GZ, de Moura AB, Quevedo J, Ferreira GC, Schuck PF, Streck EL (2018) Antioxidants reverse the changes in the cholinergic system caused by L-tyrosine Administration in Rats. Neurotox Res 34(4):769–780. Google Scholar
  34. Held PK (2006) Disorders of tyrosine catabolism. Mol Genet Metab 88:103–106Google Scholar
  35. Horn D, Barrientos A (2008) Mitochondrial copper metabolism and delivery to cytochrome c oxidase. IUBMB Life 421:429–460. Google Scholar
  36. Hughes BP (1962) A method for estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathologic sera. Clin Chim Acta 7:597–604. Google Scholar
  37. Jans JJ, de Sain-van der Velden MG, van Hasselt PM, van den Hurk DT, Vaz FM, Visser G, Verhoeven-Duif NM (2013) Supplementation with a powdered blend of PUFAs normalizes DHA and AA levels in patients with PKU. Mol Genet Metab 109(2):121–124. Google Scholar
  38. Kaur N, Chugh V, Gupta AK (2014) Essential fatty acids as functional components of foods- a review. J Food Sci Technol 51(10):2289–2303. Google Scholar
  39. Kitto GB (1969) Intra- and extramitochondrial malate dehydrogenases from chicken and tuna heart. Methods Enzymol 13:106–116. Google Scholar
  40. Kolling J, Scherer EB, Siebert C, Hansen F, Torres FV, Scaini G, Ferreira G, de Andrade RB, Gonçalves CA, Streck EL, Wannmacher CM, Wyse AT (2012) Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector? Cell Biochem Funct 31:575–584. Google Scholar
  41. Lai JC, Cooper AJ (1986) Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem 47:1376–1386. Google Scholar
  42. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231. Google Scholar
  43. Liemburg-Apers DC, Willems PH, Koopman WJ, Grefte S (2015) Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch Toxicol 89(8):1209–1226. Google Scholar
  44. Lowry OH, Rosebough NG, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  45. Macêdo LG, Carvalho-Silva M, Ferreira GK, Vieira JS, Olegário N, Gonçalves RC, Vuolo FS, Ferreira GC, Schuck PF, Dal-Pizzol F, Streck EL (2013) Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats. Neurochem Res 38(12):2625–2630. Google Scholar
  46. Macsai MS, Schwartz TL, Hinkle D, Hummel MB, Mulhern MG, Rootman D (2001) Tyrosinemia type II: nine cases of ocular signs and symptoms. Am J Ophthalmol 132:522–527. Google Scholar
  47. Mazer LM, Yi SH, Singh RH (2010) Docosahexaenoic acid status in females of reproductive age with maple syrup urine disease. J Inherit Metab Dis 33(2):121–127. Google Scholar
  48. McAnulty SR, Nieman DC, Fox-Rabinovich M, Duran V, McAnulty LS, Henson DA, Jin F, Landram MJ (2010) Effect of n-3 fatty acids and antioxidants on oxidative stress after exercise. Med Sci Sports Exerc 42:1704–1711. Google Scholar
  49. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71. Google Scholar
  50. Mitchell GA, Lambert M, Tanguay RM (1995) Hypertyrosinemia. In: Scriver CR, Beader AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 7–1077Google Scholar
  51. Mitchell GA, Grompe M, Lambert M, Tanguay RM (2001) Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. Mc Graw-Hill, New York, pp 1977–1982Google Scholar
  52. Mitchell GA, Grompe M, Lambert M, Tanguay RM (2013) Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. Mc Graw-Hill, New York. Google Scholar
  53. Morre MC, Hefti F, Wurtman RJ (1980) Regional tyrosine levels in rat brain after tyrosine administration. J Neural Transm 49:45–50Google Scholar
  54. Morrison JF (1954) The activation of aconitase by ferrous ions and reducing agents. Biochem J 58(4):685–692Google Scholar
  55. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13. Google Scholar
  56. O’Hare MC, Doonan S (1985) Purification and structural comparisons of the cytosolic and mitochondrial isoenzymes of fumarase from pig liver. Biochim Biophys Acta 827:127–134. Google Scholar
  57. Paker AM, Sunness JS, Brereton NH, Speedie LJ, Albanna L, Dharmaraj S, Moser AB, Jones RO, Raymond GV (2010) Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial. Neurology 75(9):826–830. Google Scholar
  58. Peña-Quintana L, Scherer G, Curbelo-Estévez ML, Jiménez-Acosta F, Hartmann B, Roche F, Meavilla-Olivas S, Pérez-Cerdá C, García Segarra N, Giguère Y, Huppke P, Mitchell GA, Mönch E, Trump D, Vianey-Saban C, Trimble ER, Vitoria-Miñana I, Reyes-Suárez D, Ramírez-Lorenzo T, Tugores A (2017) Tyrosinemia type II: mutation update, eleven novel mutations and description of five independent subjects with a novel founder mutation. Clin Genet 92(3):306–317. Google Scholar
  59. Plaut GWE (1969) Isocitrate dehydrogenase from bovine heart. In: Lowentein JM (ed) Methods in enzymology. Academic Press, New York, pp 34–42. Google Scholar
  60. Ramos AC, Ferreira GK, Carvalho-Silva M, Furlanetto CB, Gonçalves CL, Ferreira GC, Schuck PF, Streck EL (2013) Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats. Int J Dev Neurosci 31(5):303–307. Google Scholar
  61. Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34(6):1021–1029. Google Scholar
  62. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363Google Scholar
  63. Ribeiro CA, Sgaravatti AM, Rosa RB, Schuck PF, Grando V, Schmidt AL, Ferreira GC, Perry ML, Dutra-Filho CS, Wajner M (2008) Inhibition of brain energy metabolism by the branched-chain amino acids accumulating in maple syrup urine disease. Neurochem Res 33:114–124. Google Scholar
  64. Rigante D, Gasbarrini A, Nista EC, Candelli M (2005) Decreased mitochondrial oxidative capacity in hereditary tyrosinemia type 1. Scand J Gastroenterol 40:612–613. Google Scholar
  65. Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2004) Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32:342–349. Google Scholar
  66. Rustin P, Chretien D, Bourgeron T, Gérard B, Rötig A, Saudubray JM, Munnich A (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228:35–51. Google Scholar
  67. Salberg S, Yamakawa G, Christensen J, Kolb B, Mychasiuk R (2017) Assessment of a nutritional supplement containing resveratrol, prebiotic Fiber, and Omega-3 fatty acids for the prevention and treatment of mild traumatic brain injury in rats. Neuroscience 365:146–157. Google Scholar
  68. Sawa K, Uematsu T, Korenaga Y, Hirasawa R, Kikuchi M, Murata K, Zhang J, Gai X, Sakamoto K, Koyama T, Satoh T (2017) Krebs cycle intermediates protective against oxidative stress by modulating the level of reactive oxygen species in neuronal HT22 cells. Antioxidants (Basel) 6(1).
  69. Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP (2012) Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men. Nutr Metab 9(1):45. Google Scholar
  70. Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A (2010) Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr 169:149–164. Google Scholar
  71. Schurr A (2002) Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 41:1–8. Google Scholar
  72. Sgaravatti AM, Vargas BA, Zandoná BR, Deckmann KB, Rockenback FJ, Moraes TB, Monserrat JM, Sgarbi MB, Pederzolli CD, Wyse ATS, Wannmacher CMD, Wajner M, Dutra-Filho CS (2008) Tyrosine promotes oxidative stress in cerebral cortex of young rats. Int J Dev Neurosci 26:553–559. Google Scholar
  73. Sgaravatti AM, Magnusson AS, de Oliveira AS, Rosa AP, Mescka CP, Zanin FR, Pederzolli CD, Wyse AT, Wannmacher CM, Wajner M, Dutra-Filho CS (2009) Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex. Metab Brain Dis 24:415–425. Google Scholar
  74. Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D (2017) Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation 136(16):1459–1461. Google Scholar
  75. Smith WL (1992) Prostanoid biosynthesis and mechanism of action. Am J Physiol Ren Physiol 263(2):F181–F191. Google Scholar
  76. Soares DC, Stroparo MN, Lian YC, Takakura CY, Wolf S, Betz R, Kim CA (2017) Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome. J Inherit Metab Dis 40(3):461–462. Google Scholar
  77. Solberg R, Longini M, Proietti F, Perrone S, Felici C, Porta A, Saugstad OD, Buonocore G (2017) DHA reduces oxidative stress after perinatal asphyxia: a study in newborn piglets. Neonatology 112:1–8. Google Scholar
  78. Srere PA (1969) Citrate synthase. Methods Enzymol 13:3–11. Google Scholar
  79. Streck EL, De Prá SD, Ferro PR, Carvalho-Silva M, Gomes LM, Agostini JF, Damiani A, Andrade VM, Schuck PF, Ferreira GC, Scaini G (2017) Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II. Mol Cell Biochem 435:207–214. Google Scholar
  80. Teodorak BP, Scaini G, Carvalho-Silva M, Gomes LM, Teixeira LJ, Rebelo J, Prá SD, Zeni N, Schuck PF, Ferreira GC, Streck EL (2017) Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L-tyrosine. Metab Brain Dis 32(2):557–564. Google Scholar
  81. Tretter L, Adam-Vizi V (2004) Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase. J Neurosci 24:7771–7778. Google Scholar
  82. Valikhani M, Akhyani M, Jafari AK, Barzegari M, Toosi S (2006) Oculocutaneous tyrosinaemia or tyrosinaemia type 2: a case report. J Eur Acad Dermatol Venereol 20(5):591–594. Google Scholar
  83. Vlaardingerbroek H, Hornstra G, de Koning TJ, Smeitink JA, Bakker HD, de Klerk HB, Rubio-Gozalbo ME (2006) Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism. Mol Genet Metab 88(2):159–165. Google Scholar
  84. Wall R, Ross RP, Fitzgerald GF, Stanton C (2010) Fatty acids from fish: the antiinflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 68:280–289. Google Scholar
  85. Wiest EF, Walsh-Wilcox MT, Walker MK (2017) Omega-3 polyunsaturated fatty acids protect against cigarette smoke-induced oxidative stress and vascular dysfunction. Toxicol Sci 156(1):300–310. Google Scholar
  86. Wu A, Ying Z, Gomez-Pinilla F (2008) Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 155(3):751–759. Google Scholar
  87. Wurtman RJ (2008) Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metab Clin Exp 57(10):S6–S10. Google Scholar
  88. Zhang W, Li P, Hu X, Zhang F, Chen J, Gao Y (2011) Omega-3 polyunsaturated fatty acids in the brain: metabolism and neuroprotection. Front Biosci 16:2653–2670Google Scholar
  89. Zribi H, Souissi A, Azzouz H, Tebib N, Mokni M (2016) Richner-Hanhart syndrome. Presse Med 45(2):264–265. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Milena Carvalho-Silva
    • 1
    • 2
  • Lara M. Gomes
    • 1
    • 2
  • Maria L. Gomes
    • 1
    • 2
  • Bruna K. Ferreira
    • 1
    • 2
  • Patricia F. Schuck
    • 1
    • 2
  • Gustavo C. Ferreira
    • 3
  • Felipe Dal-Pizzol
    • 4
  • Jade de Oliveira
    • 2
  • Giselli Scaini
    • 1
    • 5
  • Emilio L. Streck
    • 1
    • 2
    Email author
  1. 1.Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da SaúdeUniversidade do Extremo Sul Catarinense (UNESC)CriciúmaBrazil
  2. 2.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da SaúdeUniversidade do Extremo Sul Catarinense (UNESC)CriciúmaBrazil
  3. 3.Laboratório de Neuroenergética e Erros Inatos do Metabolismo, Instituto de Biofísica Carlos ChagasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  4. 4.Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  5. 5.Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolThe University of Texas Health Science Center at Houston (UTHealth)HoustonUSA

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