Genes & Nutrition

, Volume 7, Issue 3, pp 447–458 | Cite as

Partial rescue of Rett syndrome by ω-3 polyunsaturated fatty acids (PUFAs) oil

  • Claudio De Felice
  • Cinzia Signorini
  • Thierry Durand
  • Lucia Ciccoli
  • Silvia Leoncini
  • Maurizio D’Esposito
  • Stefania Filosa
  • Camille Oger
  • Alexandre Guy
  • Valérie Bultel-Poncé
  • Jean-Marie Galano
  • Alessandra Pecorelli
  • Laura De Felice
  • Giuseppe Valacchi
  • Joussef Hayek
Research Paper


Evidence of enhanced oxidative stress (O.S.) and lipid peroxidation has been reported in patients with Rett syndrome (RTT), a relatively rare neurodevelopmental disorder progressing in 4-stages, and mainly caused by loss-of-function mutations in the methyl-CpG-binding protein 2. No effective therapy for preventing or arresting the neurologic regression in the disease in its various clinical presentations is available. Based on our prior evidence of enhanced O.S. and lipid peroxidation in RTT patients, herein we tested the possible therapeutic effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs), known antioxidants with multiple effects, on the clinical symptoms and O.S. biomarkers in the earliest stage of RTT. A total of 20 patients in stage I were randomized (n = 10 subjects per arm) to either oral supplementation with ω-3 PUFAs-containing fish oil (DHA: 72.9 ± 8.1 mg/kg b.w./day; EPA: 117.1 ± 13.1 mg/kg b.w./day; total ω-3 PUFAs: 246.0 ± 27.5 mg/kg b.w./day) for 6 months or no treatment. Primary outcomes were potential changes in clinical symptoms, with secondary outcomes including variations for five O.S. markers in plasma and/or erythrocytes (nonprotein bound iron, F2-dihomo-isoprostanes, F3-isoprostanes, F4-neuroprostanes, and F2-isoprostanes). A significant reduction in the clinical severity (in particular, motor-related signs, nonverbal communication deficits, and breathing abnormalities) together with a significant decrease in all the examined O.S. markers was observed in the ω-3 PUFAs supplemented patients, whereas no significant changes were evidenced in the untreated group. For the first time, these findings strongly suggest that a dietary intervention in this genetic disease at an early stage of its natural history can lead to a partial clinical and biochemical rescue.


Rett syndrome MeCP2 Oxidative Stress ω-3 polyunsaturated fatty acids Isoprostanes Nonprotein bound iron Antioxidants 



Arachidonic acid


Adrenic acid


Cyclin-dependent kinase-like 5




Forkhead box G1


Gas chromatography/negative ion chemical ionization tandem mass spectrometry




Methyl-CpG-binding protein 2


Nonprotein bound iron


Oxidative stress


Rett syndrome

Supplementary material

Supplementary material movie 1 (MPG 215 mb)


  1. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188PubMedCrossRefGoogle Scholar
  2. Anderson BM, Ma DWL (2009) Are all n-3 polyunsaturated fatty acids created equal? Lipids Health Dis 8:33PubMedCrossRefGoogle Scholar
  3. Ariani F, Hayek G, Rondinella D, Artuso R, Mencarelli MA, Spanhol-Rosseto A, Pollazzon M, Buoni S, Spiga O, Ricciardi S, Meloni I, Longo I, Mari F, Broccoli V, Zappella M, Renieri A (2008) FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 83:89–93PubMedCrossRefGoogle Scholar
  4. Arnold C, Markovic M, Blossey K, Wallukat G, Fischer R, Dechend R, Konkel A, von Schacky C, Luft FC, Muller DN, Rothe M, Schunck WH (2010) Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of 3 fatty acids. J Biol Chem 285:32720–32733PubMedCrossRefGoogle Scholar
  5. Ballas N, Lioy DT, Grunseich C, Mandel G (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 12:311–317PubMedCrossRefGoogle Scholar
  6. Bazan NG (2007) Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 10:136–141PubMedCrossRefGoogle Scholar
  7. Belayev L, Marcheselli VL, Khoutorova L, Rodriguez de Turco EB, Busto R, Ginsberg MD, Bazan NG (2005) Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke 36:118–123PubMedCrossRefGoogle Scholar
  8. Belayev L, Khoutorova L, Atkins KD, Bazan NG (2009) Robust docosahexaenoic acid-mediated neuroprotection in a rat model of transient, focal cerebral ischemia. Stroke 40:3121–3126PubMedCrossRefGoogle Scholar
  9. Ben-Shachar S, Chahrour M, Thaller C, Shaw CA, Zoghbi HY (2009) Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet 18:2431–2442PubMedCrossRefGoogle Scholar
  10. Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505S–1519SPubMedGoogle Scholar
  11. Calder PC, Yaqoob P (2009) Understanding omega-3 polyunsaturated fatty acids. Postgrad Med 121:148–157PubMedCrossRefGoogle Scholar
  12. Cappa M, Bizzarri C, Vollono C, Petroni A, Banni S (2011) Adrenoleukodystrophy. Endocr Dev 20:149–160PubMedCrossRefGoogle Scholar
  13. Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56:422–437PubMedCrossRefGoogle Scholar
  14. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–1229PubMedCrossRefGoogle Scholar
  15. Chang CY, Ke DS, Chen JY (2009) Essential fatty acids and human brain. Acta Neurol Taiwan 18:231–241PubMedGoogle Scholar
  16. Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Lu HC, Heintz N, Ekker M, Rubenstein JL, Noebels JL, Rosenmund C, Zoghbi HY (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468:263–269PubMedCrossRefGoogle Scholar
  17. Chapkin RS, McMurray DN, Davidso LA, Patil BS, Fan YY, Lupton JR (2008) Bioactive dietary long-chain fatty acids: emerging mechanisms of action. Br J Nutr 100:1152–1157PubMedCrossRefGoogle Scholar
  18. Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH, Hamdy RC, Xu X, Liu CF (2011) Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett 499:181–185PubMedCrossRefGoogle Scholar
  19. Cobb S, Guy J, Bird A (2010) Reversibility of functional deficits in experimental models of Rett syndrome. Biochem Soc Trans 38:498–506PubMedCrossRefGoogle Scholar
  20. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, David Sweatt J, Zoghbi HY (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13:2679–2689PubMedCrossRefGoogle Scholar
  21. Comporti M, Signorini C, Buonocore G, Ciccoli L (2002) Iron release, oxidative stress and erythrocyte ageing. Free Radic Biol Med 32:568–576PubMedCrossRefGoogle Scholar
  22. Comporti M, Signorini C, Arezzini B, Vecchio D, Monaco B, Gardi C (2008) F2-isoprostanes are not just markers of oxidative stress. Free Radic Biol Med 44:247–256PubMedCrossRefGoogle Scholar
  23. de Assis AM, Rech A, Longoni A, Rotta LN, Denardin CC, Pasquali MA, Souza DO, Perry ML, Moreira JC (2012) Ω3-Polyunsaturated fatty acids prevent lipoperoxidation, modulate antioxidant enzymes, and reduce lipid content but do not alter glycogen metabolism in the livers of diabetic rats fed on a high fat thermolyzed diet. Mol Cell Biochem 361:151–160PubMedCrossRefGoogle Scholar
  24. De Felice C, Ciccoli L, Leoncini S, Signorini C, Rossi M, Vannuccini L, Guazzi G, Latini G, Comporti M, Valacchi G, Hayek J (2009) Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med 47:440–448PubMedCrossRefGoogle Scholar
  25. De Felice C, Signorini C, Durand T, Oger C, Guy A, Bultel-Poncé V, Galano JM, Ciccoli L, Leoncini S, D’Esposito M, Filosa S, Pecorelli A, Valacchi G, Hayek J (2011) F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome. J Lipid Res 52:2287–2297PubMedCrossRefGoogle Scholar
  26. Deckelbaum RJ, Worgall TS, Seo T (2006) n-3 fatty acids and gene expression. Am J Clin Nutr 83:1520S–1525SPubMedGoogle Scholar
  27. 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 10:142PubMedCrossRefGoogle Scholar
  28. Fourcade S, López-Erauskin J, Galino J, Duval C, Naudi A, Jove M, Kemp S, Villarroya F, Ferrer I, Pamplona R, Portero-Otin M, Pujol A (2008) Early oxidative damage underlying neurodegeneration in X- adrenoleukodystrophy. Hum Mol Genet 17:1762–1773PubMedCrossRefGoogle Scholar
  29. Galino J, Ruiz M, Fourcade S, Schlüter A, López-Erauskin J, Guilera C, Jove M, Naudi A, García-Arumí E, Andreu AL, Starkov AA, Pamplona R, Ferrer I, Portero-Otin M, Pujol A (2011) Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy. Antioxid Redox Signal 15:2095–2107PubMedCrossRefGoogle Scholar
  30. Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y, Masumura S (1999) Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 93:237–241PubMedCrossRefGoogle Scholar
  31. Guy J, Gan J, Selfridge J, Cobb S, Bird A (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315:1143–1147PubMedCrossRefGoogle Scholar
  32. Guy J, Cheval H, Selfridge J, Bird A (2011) The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 27:631–652PubMedCrossRefGoogle Scholar
  33. Hagberg B, Aicardi J, Dias K, Ramos O (1983) A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 14:471–479PubMedCrossRefGoogle Scholar
  34. Halliwell B, Gutteridge J (1999) Free radicals, other reactive species and disease. In: Halliwell B, Gutteridge J (eds) Free radicals in biology and medicine. Clarendon Press, Oxford, pp 617–783Google Scholar
  35. Johnson RA, Lam M, Punzo AM, Li H, Lin BR, Ye K, Mitchell GS, Chang Q (2011) 7,8-dihydroxyflavone (7,8-DHF) exhibits therapeutic efficacy in a mouse model of Rett syndrome. J Appl Physiol. doi:10.1152/japplphysiol.01361
  36. Jump DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277:8755–8758PubMedCrossRefGoogle Scholar
  37. Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brot N, Fitzgerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC (2005) Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med 38:698–710PubMedCrossRefGoogle Scholar
  38. Kawashima H, Nishimata S, Ishii C, Yamanaka G, Kashiwagi Y, Takekuma K, Hoshika A, Watanabe Y (2011) New treatment of free-radical scavenger in adrenoleukodystrophy. J Clin Pharm Ther 36:412–415PubMedCrossRefGoogle Scholar
  39. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106:2747–2757Google Scholar
  40. Kron M, Müller M (2010) Impaired hippocampal Ca2+ homeostasis and concomitant K+ channel dysfunction in a mouse model of Rett syndrome during anoxia. Neuroscience 171:300–315PubMedCrossRefGoogle Scholar
  41. Leoncini S, De Felice C, Signorini C, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J (2011) Oxidative stress in Rett syndrome: natural history, genotype, and variants. Redox Rep 16:145–153PubMedCrossRefGoogle Scholar
  42. Lien EL (2009) Toxicology and safety of DHA. Prostaglandins Leukot Essent Fatty Acids 81:125–132PubMedCrossRefGoogle Scholar
  43. López-Erauskin J, Fourcade S, Galino J, Ruiz M, Schlüter A, Naudi A, Jove M, Portero-Otin M, Pamplona R, Ferrer I, Pujol A (2011) Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann Neurol 70:84–92PubMedCrossRefGoogle Scholar
  44. Macdonald JL, Verster A, Berndt A, Roskams AJ (2010) MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons. Mol Cell Neurosci 44:55–67PubMedCrossRefGoogle Scholar
  45. Maezawa I, Swanberg S, Harvey D, LaSalle JM, Jin LW (2009) Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 29:5051–5061PubMedCrossRefGoogle Scholar
  46. Mahmood A, Bibat G, Zhan AL, Izbudak I, Farage L, Horska A, Mori S, Naidu S (2010) White matter impairment in Rett syndrome: diffusion tensor imaging study with clinical correlations. AJNR Am J Neuroradiol 31:295–299PubMedCrossRefGoogle Scholar
  47. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–539PubMedCrossRefGoogle Scholar
  48. Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N (2005) CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 14:1935–1946PubMedCrossRefGoogle Scholar
  49. Mas E, Woodman RJ, Burke V, Puddey IB, Beilin LJ, Durand T, Mori TA (2010) The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes: Results from two placebo-controlled interventions. Free Radic Res 44:983–990PubMedCrossRefGoogle Scholar
  50. Mastroeni R, Bensadoun JC, Charvin D, Aebischer P, Pujol A, Raoul C (2009) Insulin-like growth factor-1 and neurotrophin-3 gene therapy prevents motor decline in an X-linked adrenoleukodystrophy mouse model. Ann Neurol 66:117–122PubMedCrossRefGoogle Scholar
  51. Matarazzo MR, De Bonis ML, Vacca M, Della Ragione F, D’Esposito M (2009) Lessons from two human chromatin diseases, ICF syndrome and Rett syndrome. Int J Biochem Cell Biol 41:117–126PubMedCrossRefGoogle Scholar
  52. McGahon BM, Martin DS, Horrobin DF, Lynch MA (1999) Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids. Neuroscience 94:305–314PubMedCrossRefGoogle Scholar
  53. McNamara RK (2010) DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders. J Nutr 140:864–868PubMedCrossRefGoogle Scholar
  54. Montine KS, Quinn JF, Zhang J, Fessel JP, Roberts LJ 2nd, Morrow JD, Montine TJ (2004) Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem Phys Lipids 128:117–124PubMedCrossRefGoogle Scholar
  55. Montuschi P, Barnes PJ, Roberts LJ (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J 18:1791–1800PubMedCrossRefGoogle Scholar
  56. Morrow JD, Roberts LJ (1997) The isoprostanes: unique bioactive products of lipid peroxidation. Prog Lipid Res 36:1–21PubMedCrossRefGoogle Scholar
  57. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387PubMedCrossRefGoogle Scholar
  58. Naidu S, Johnston MV (2011) Neurodevelopmental disorders: clinical criteria for Rett syndrome. Nat Rev Neurol 7:312–314PubMedCrossRefGoogle Scholar
  59. Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG (2008) Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 70:1313–1321PubMedCrossRefGoogle Scholar
  60. Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK (2010) Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol 68:944–950PubMedCrossRefGoogle Scholar
  61. Nourooz-Zadeh J (2008) Key issues in F2-isoprostane analysis. Biochem Soc Trans 36:1060–1065PubMedCrossRefGoogle Scholar
  62. Nourooz-Zadeh J, Gopaul NK, Barrow S, Mallet AI, Anggard EE (1995) Analysis of F2-isoprostanes as indicators of non-enzymatic lipid peroxidation in vivo by gas chromatography-mass spectrometry: development of a solid-phase extraction procedure. J Chromatogr B Biomed Appl 667:199–208PubMedCrossRefGoogle Scholar
  63. Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM (2007) Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 27:10912–10917PubMedCrossRefGoogle Scholar
  64. Pecorelli A, Ciccoli L, Signorini C, Leoncini S, Giardini A, D’Esposito M, Filosa S, Hayek J, De Felice C, Valacchi G (2011) Increased levels of 4HNE-protein plasma adducts in Rett syndrome. Clin Biochem 44:368–371PubMedCrossRefGoogle Scholar
  65. Rett A (1966) On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 116:723–726PubMedGoogle Scholar
  66. Roberts LJ, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, Dettbarn WD, Morrow JD (1998) Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 273:13605–13612PubMedCrossRefGoogle Scholar
  67. Roux JC, Dura E, Moncla A, Mancini J, Villard L (2007) Treatment with desipramine improbe breathing and survival in a mouse model for Rett syndrome. Eur J Neurosci 25:1915–1922PubMedCrossRefGoogle Scholar
  68. Sastry PS (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24:69–176PubMedCrossRefGoogle Scholar
  69. Schmitz G, Ecker J (2008) The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47:147–155PubMedCrossRefGoogle Scholar
  70. Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176:1848–1859PubMedGoogle Scholar
  71. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361PubMedCrossRefGoogle Scholar
  72. Signorini C, Comporti M, Giorgi G (2003) Ion trap tandem mass spectrometric determination of F2-isoprostanes. J Mass Spectrom 38:1067–1074PubMedCrossRefGoogle Scholar
  73. Signorini C, Ciccoli L, Leoncini S, Carloni S, Perrone S, Comporti M, Balduini W, Buonocore G (2009) Free iron, total F2-isoprostanes and total F4-neuroprostanes in a model of neonatal hypoxic-ischemic encephalopathy: neuroprotective effect of melatonin. J Pineal Res 46:148–154PubMedCrossRefGoogle Scholar
  74. Signorini C, De Felice C, Leoncini S, Giardini A, D’Esposito M, Filosa S, Della Ragione F, Rossi M, Pecorelli A, Valacchi G, Ciccoli L, Hayek J (2011) F4-neuroprostanes mediate neurological severity in Rett syndrome. Clin Chim Acta 412:1399–1406PubMedCrossRefGoogle Scholar
  75. Soderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26:421–425PubMedCrossRefGoogle Scholar
  76. Sprecher H, VanRollins M, Sun F, Wyche A, Needleman P (1982) Dihomo-prostaglandins and -thromboxane. A prostaglandin family from adrenic acid that may be preferentially synthesized in the kidney. J Biol Chem 257:3912–3918PubMedGoogle Scholar
  77. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M (2009) Partial reversal of Rett syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA 106:2029–2034PubMedCrossRefGoogle Scholar
  78. VanRollins M, Woltjer RL, Yin H, Morrow JD, Montine TJ (2008) F2-dihomo-isoprostanes arise from free radical attack on adrenic acid. J Lipid Res 49:995–1005PubMedCrossRefGoogle Scholar
  79. Viemari JC, Roux JC, Tryba AK, Saywell V, Burnet H, Pena F, Zanella S, Bevengut M, Barthelemy-Requin M, Herzing LB, Moncla A, Mancini J, Ramirez JM, Villard L, Hilaire G (2005) Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 25:11521–11530PubMedCrossRefGoogle Scholar
  80. Wada M, DeLong CJ, Hong YH, Rieke CJ, Song I, Sidhu RS, Yuan C, Warnock M, Schmaier AH, Yokoyama C, Smyth EM, Wilson SJ, FitzGerald GA, Garavito RM, de Sui X, Regan JW, Smith WL (2007) Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem 282:22254–22266PubMedCrossRefGoogle Scholar
  81. Wood LG, Gibson PG, Garg ML (2003) Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur Respir J 21:177–186PubMedCrossRefGoogle Scholar
  82. Xiao YF, Sigg DC, Leaf A (2005) The antiarrhythmic effect of n-3 polyunsaturated fatty acids: modulation of cardiac ion channels as a potential mechanism. J Membr Biol 206:141–154PubMedCrossRefGoogle Scholar
  83. Yin H, Porter NA (2005) New insights regarding the autoxidation of polyunsaturated fatty acids. Antioxid Redox Signal 7:170–184PubMedCrossRefGoogle Scholar
  84. Yin H, Liu W, Goleniewska K, Porter NA, Morrow JD, Peebles RS (2009) Dietary supplementation of omega-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation. Free Radic Biol Med 47:622–628PubMedCrossRefGoogle Scholar
  85. 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 17:2653–2670PubMedCrossRefGoogle Scholar
  86. Zoghbi HY (2009) Rett syndrome: what do we know for sure? Nat Neurosci 12:239–240PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Claudio De Felice
    • 1
  • Cinzia Signorini
    • 2
  • Thierry Durand
    • 3
  • Lucia Ciccoli
    • 2
  • Silvia Leoncini
    • 2
  • Maurizio D’Esposito
    • 4
    • 5
  • Stefania Filosa
    • 4
    • 5
  • Camille Oger
    • 3
  • Alexandre Guy
    • 3
  • Valérie Bultel-Poncé
    • 3
  • Jean-Marie Galano
    • 3
  • Alessandra Pecorelli
    • 2
  • Laura De Felice
    • 6
  • Giuseppe Valacchi
    • 7
    • 8
  • Joussef Hayek
    • 9
  1. 1.Neonatal Intensive Care UnitUniversity Hospital Azienda Ospedaliera Universitaria Senese (AOUS) of Siena, S. M. Le Scotte General HospitalSienaItaly
  2. 2.Department of Pathophysiology, Experimental Medicine and Public HealthUniversity of SienaSienaItaly
  3. 3.Institut des Biomolécules Max Mousseron (IBMM)UMR 5247 CNRS, UM I, UM IIMontpellierFrance
  4. 4.Institute of Genetics and Biophysics “Adriano Buzzati Traverso” CNRNapoliItaly
  5. 5.IRCCS NeuromedPozzilliItaly
  6. 6.Multimedia Content Design Master CourseUniversity of FlorenceFlorenceItaly
  7. 7.Department of Evolutionary BiologyUniversity of FerraraFerraraItaly
  8. 8.Department of Food and NutritionKyung Hee UniversitySeoulKorea
  9. 9.Child Neuropsychiatry UnitUniversity Hospital, AOUSSienaItaly

Personalised recommendations