Fatty Acids and Autism Spectrum Disorders: The Rett Syndrome Conundrum

DOI: 10.4236/fns.2013.49A1012   PDF   HTML   XML   3,715 Downloads   5,416 Views   Citations

Abstract

Autism spectrum disorders (ASDs) are epidemically explosive clinical entities, but their pathogenesis is still unclear and a definitive cure does not yet exist. Rett syndrome (RTT) is a rare genetically determined cause of autism linked to mutations in the X-linked MeCP2 gene or, more rarely, in CDKL5 or FOXG1. A wide phenotypical heterogeneity is a known feature of the disease. Although several studies have focused on the molecular genetics and possible protein changes at different levels, to date very little attention has been paid to fatty acids in this disease, which could be considered as a natural paradigm for the ASDs. To this regard, a quite enigmatic feature of the disease is the evidence in the affected patients of an extensive peroxidation of polyunsaturated fatty acids (arachidonic acid, AA, docosaexahenoic acid, DHA, adrenic acid, AdA and, to a lesser extent, eicosapentaenoic acid, EPA), in contrast with amelioration of the redox changes and phenotypical severity following the supplementation of some of those same fatty acids (DHA + EPA). Therefore, fatty acids may represent a kind of Janus Bifrons in the particular context of RTT. Here, we propose a rational explanation for this apparent “fatty acid paradox” in RTT. A better understanding of this paradox could also be of help to get a better insight into the complex mechanism of action for polyunsaturated fatty acids in health and disease.

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C. Felice, C. Signorini, S. Leoncini, A. Pecorelli, T. Durand, J. Galano, V. Bultel-Poncé, A. Guy, C. Oger, G. Zollo, G. Valacchi, L. Ciccoli and J. Hayek, "Fatty Acids and Autism Spectrum Disorders: The Rett Syndrome Conundrum," Food and Nutrition Sciences, Vol. 4 No. 9A, 2013, pp. 71-75. doi: 10.4236/fns.2013.49A1012.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] M. Zeman, R. Jirak, M. Vecka, J. Raboch and A. Zak, “n-3 Polyunsaturated Fatty Acids in Psychiatric Diseases: Mechanisms and Clinical Data,” Neuro Endocrinology Letters, Vol. 33, No. 8, 2012, pp. 736-748.
[2] J. P. Schuchardt, M. Huss, M. Stauss-Grabo and A. Hahn, “Significance of Long-Chain Polyunsaturated Fatty Acids (PUFAs) for the Development and Behaviour of Chil dren,” European Journal of Pediatrics, Vol. 169, No. 2, 2010, pp. 149-164. doi:10.1007/s00431-009-1035-8
[3] P. L. Prior and J. C. Galduróz, “(n-3) Fatty Acids: Mo lecular Role and Clinical Uses in Psychiatric Disorders,” Advances in Nutrition, Vol. 3, No. 3, 2012, pp. 257-265. doi:10.3945/an.111.001693
[4] B. Hagberg, J. Aicardi, K. Dias and O. Ramos, “A Pro gressive Syndrome of Autism, Dementia, Ataxia, and Loss of Purposeful Hand Use in Girls: Rett’s Syndrome: Report of 35 Cases,” Annals of Neurology, Vol. 14, No. 4, 1983, pp. 471-479. doi:10.1002/ana.410140412
[5] T. Bienvenu, C. Philippe, N. De Roux, M. Raynaud, J. P. Bonnefond, L. Pasquier, G. Lesca, J. Mancini, P. Jon veaux, A. Moncla, J. Feingold, J. Chelly and L. Villard, “The incidence of Rett Syndrome in France,” Pediatric Neurology, Vol. 34, No. 5, 2006, pp. 372-375. doi:10.1016/j.pediatrneurol.2005.10.013
[6] H. Y. Zoghbi, “MeCP2 Dysfunction in Humans and Mice,” Journal of Child Neurology, Vol. 20, No. 9, 2005, pp. 736-740. doi:10.1177/08830738050200090701
[7] J. L. Neul, W. E. Kaufmann, D. G. Glaze, J. Christodou lou, A. J. Clarke, N. Bahi-Buisson, H. Leonard, M. E. Bailey, N. C. Schanen, M. Zappella, A. Renieri, P. Hup pke, A. K. Percy and Rett Search Consortium, “Rett Syn drome: Revised Diagnostic Criteria and Nomenclature,” Annals of Neurology, Vol. 68, No. 6, 2010, pp. 944-950.
[8] E. Grillo, C. Lo Rizzo, L. Bianciardi, V. Bizzarri, M. Baldassarri, O. Spiga, S. Furini, C. De Felice, C. Signorini, S. Leoncini, A. Pecorelli, L. Ciccoli, M. A. Mencarelli, J. Hayek, I. Meloni, F. Ariani, F. Mari and A. Renieri, “Revealing the Complexity of a Monogenic Disease: Rett Syndrome Exome Sequencing,” Public Library of Science One, Vol 8, No. 2, 2013, Article ID: e56599.
[9] K. Miyake, C. Yang, Y. Minakuchi, K. Ohori, M. Soutome, T. Hirasawa, Y. Kazuki, N. Adachi, S. Suzuki, M. Itoh, Y. I. Goto, T. Andoh, H. Kurosawa, M. Oshimura, M. Sasaki, A. Toyoda and T. Kubota, “Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome,” Public Library of Science One, Vol. 8, No. 6, 2013, Article ID: e66729.
[10] J. Guy, H. Cheval, J. Selfridge and A. Bird, “The Role of MeCP2 in the Brain,” Annual Review of Cell and Devel opmental Biology, Vol. 27, 2011, pp. 631-652. doi:10.1146/annurev-cellbio-092910-154121
[11] J. Guy, J. Gan, J. Selfridge, S, Cobb and A. Bird, “Reversal of Neurological Defects in a Mouse Model of Rett Syndrome,” Science, Vol. 315, No. 5815, 2007, pp. 1143-1147. doi:10.1126/science.1138389
[12] A. Lekman, B. Hagberg and L. Svennerholm, “Altered Cerebellar Ganglioside Pattern in Rett Syndrome,” Neu rochemistry International, Vol. 19, No. 4, 1991, pp. 505 509. doi:10.1016/0197-0186(91)90068-O
[13] A. Y. Lekman, B. A. Hagberg and L. T. Svennerholm, “Membrane Cerebral Lipids in Rett Syndrome,” Pediatric Neurology, Vol. 7, No. 3, 1991, pp. 186-190. doi:10.1016/0887-8994(91)90082-V
[14] A. Y. Lekman, B. A. Hagberg and L. T. Svennerholm, “Cerebrospinal Fluid Gangliosides in Patients with Rett Syndrome and Infantile Neuronal Ceroid Lipofuscinosis,” European Journal of Paediatric Neurology, Vol. 3, No. 3, 1999, pp. 119-123. doi:10.1016/S1090-3798(99)90099-5
[15] A. Oldfors, P. Sourander, D. L. Armstrong, A. K. Percy, I. Witt-Engerstrom and B. A. Hagberg, “Rett Syndrome: Cerebellar Pathology,” Pediatric Neurology, Vol. 6, No. 5, pp. 310-314. doi:10.1016/0887-8994(90)90022-S
[16] T. J. Stradomska, A. Tylki-Szymańska and Z. Bent kowski, “Very Long-Chain Fatty Acids in Rett Syn drome,” European Journal of Pediatrics, Vol. 158, No. 3, 1999, pp. 226-229.
doi:10.1007/s004310051055
[17] L. Burd, R. Kemp, H. Knull and D. Loveless, “A Review of the Biochemical Pathways Studied and Abnormalities Reported in the Rett Syndrome,” Brain & Development, Vol. 12, No. 4, 1990, pp. 444-448. doi:10.1016/S0387-7604(12)80081-7
[18] P. Blardi, A. de Lalla, T. D’Ambrogio, M. Zappella, G. Cevenini, L. Ceccatelli, A. Auteri and J. Hayek, “Rett Syndrome and Plasma Leptin Levels,” The Journal of Pediatrics, Vol. 150, No. 1, 2007, pp. 37-39. doi:10.1016/j.jpeds.2006.10.061
[19] P. Blardi, A. de Lalla, T. D’Ambrogio, G. Vonella, L. Ceccatelli, A. Auteri and J. Hayek, “Long-Term Plasma Levels of Leptin and Adiponectin in Rett Syndrome,” Clinical Endocrinology (Oxford), Vol. 70, No. 5, 2009, pp. 706-709. doi:10.1111/j.1365-2265.2008.03386.x
[20] K. J. Motil, R. Schultz, B. Brown, D. C. Glaze and A. K. Percy, “Altered Energy Balance May Account for Growth Failure in Rett Syndrome,” Journal of Child Neurology, Vol. 9, No. 3, 1994, pp. 315-319. doi:10.1177/088307389400900319
[21] F. Carbone, C. La Rocca and G. Matarese, “Immunologi cal Functions of Leptin and Adiponectin,” Biochimie, Vol. 94, No. 10, 2012, pp. 2082-2088. doi:10.1016/j.biochi.2012.05.018
[22] C. Sticozzi, G. Belmonte, A. Pecorelli, F. Cervellati, S. Leoncini, C. Signorini, L. Ciccoli, C. De Felice, J. Hayek and G. Valacchi, “Scavenger Receptor B1 Post-Transla tional Modifications in Rett Syndrome,” FEBS Letters, 2013 (in press). doi:10.1016/j.febslet.2013.05.042
[23] C. De Felice, C. Signorini, S. Leoncini, A. Pecorelli, T. Durand, G. Valacchi, L. Ciccoli and J. Hayek, “The Role of Oxidative Stress in Rett Syndrome: An Overview,” Annals of the New York Academy of Sciences, Vol. 1259, 2012, pp. 121-135. doi:10.1111/j.1749-6632.2012.06611.x
[24] S. Leoncini, C. De Felice, C. Signorini, A. Pecorelli, T. Durand, G. Valacchi, L. Ciccoli and J. Hayek, “Oxidative Stress in Rett Syndrome: Natural History, Genotype, and Variants,” Redox Report, Vol. 16, No. 4, 2011, pp. 145-153. doi:10.1179/1351000211Y.0000000004
[25] C. Signorini, C. De Felice, S. Leoncini, A. Giardini, M. D’Esposito, S. Filosa, F. Della Ragione, M. Rossi, A. Pecorelli, G. Valacchi, L. Ciccoli and J. Hayek, “F4 Neuroprostanes Mediate Neurological Severity in Rett Syndrome,” Clinica Chimica Acta, Vol. 412, No. 15-16, 2011, pp. 1399-1406.
doi:10.1016/j.cca.2011.04.016
[26] C. De Felice, C. Signorini, T. Durand, C. Oger, A. Guy, V. Bultel-Poncé, J-M Galano, L. Ciccoli, S. Leoncini, M. D’Esposito, S. Filosa, A. Pecorelli, G. Valacchi and J. Hayek, “F2-Dihomo-Isoprostanes as Potential Early Bio markers of Lipid Oxidative Damage in Rett Syndrome,” Journal of Lipid Research, Vol. 52, No. 12, 2011, pp. 2287-2297. doi:10.1194/jlr.P017798
[27] C. Signorini, C. De Felice, T. Durand, C. Oger, J.-M. Galano, S. Leoncini, A. Pecorelli, G. Valacchi, L. Ciccoli and J. Hayek, “Isoprostanes and 4-Hydroxy-2-nonenal: Markers or Mediators of Disease? Focus on Rett Syn drome as a Model of Autism Spectrum Disorder,” Oxida tive Medicine and Cellular Longevity, 2013, Article ID: 343824. doi:10.1155/2013/343824
[28] J.-M. Galano, E. Mas, A. Barden, T. A. Mori, C. Signorini, C. De Felice, A. Barrett, C. Opere, E. Pinot, E. Schwedhelm, R. Benndorf, J. Roy, J. Y. Le Guennec, C. Oger and T. Durand, “Isoprostanes and Neuroprostanes: Total Synthesis, Biological Activity and Biomarkers of Oxidative Stress in Humans,” Prostaglandins & Other Lipid Mediators, 2013 (in press). doi:10.1016/j.prostaglandins.2013.04.003
[29] T. Durand, C. De Felice, C. Signorini, C. Oger, V. Bultel Poncé, A. Guy, J.-M. Galano, S. Leoncini, L. Ciccoli, A. Pecorelli, G. Valacchi and J. Hayek, “F2-Dihomo-Iso prostanes and Brain White Matter Damage in Stage 1 Rett Syndrome,” Biochimie, Vol. 95, No. 1, 2013, pp. 86-90.
doi:10.1016/j.biochi.2012.09.017
[30] C. De Felice, C. Signorini, T. Durand, L. Ciccoli, S. Leoncini, M. D’Esposito, S. Filosa, C. Oger, A. Guy, V. Bultel-Poncé, J.-M. Galano, A. Pecorelli, L. De Felice, G. Valacchi and J. Hayek, “Partial Rescue of Rett Syndrome by ω-3 Polyunsaturated Fatty Acids (PUFAs) Oil,” Genes & Nutrition, Vol. 7, No. 3, 2012, pp. 447-458. doi:10.1007/s12263-012-0285-7
[31] C. N. Serhan, M. Arita, S. Hong and K. Gotlinger, “Re solvins, Docosatrienes, and Neuroprotectins, Novel Omega-3-Derived Mediators, and Their Endogenous As pirin-Triggered Epimers,” Lipids, Vol. 39, No. 11, 2004, pp. 1125-1132. doi:10.1007/s11745-004-1339-7
[32] C. N. Serhan, “Systems Approach with Inflammatory Exudates Uncovers Novel Anti-Inflammatory and Pro Resolving Mediators,” Prostaglandins, Leukotrienes, and Essential Fatty Acids, Vol. 79, No. 3-5, 2008, pp. 157 163. doi:10.1016/j.plefa.2008.09.012
[33] C. Arnold, M. Markovic, K. Blossey, G. Wallukat, R. Fischer, R. Dechend, A. Konkel, C. von Schacky, F. C. Luft, D. N. Muller, M. Rothe and W. H. Schunck, “Arachidonic Acid-Metabolizing Cytochrome P450 Enzymes Are Targets of 3 Fatty Acids,” The Journal of Biological Chemistry, Vol. 285, No. 43, 2010, pp. 32720-32733. doi:10.1074/jbc.M110.118406
[34] C. M. Buchovecky, S. D. Turley, H. M. Brown, S. M. Kyle, J. G. McDonald, B. Liu, A. A. Pieper, W. Huang, D. M. Katz, D. W. Russell, J. Shendure and M. J. Justice, “A Suppressor Screen Mecp2 Mutant Mice Implicates Cho lesterol Metabolism in Rett Syndrome,” Nature Genetics, 2013 (in press). doi:10.1038/ng.2714
[35] M. Ewang-Emukowhate and A. S. Wierzbicki “Lipid Lowering Agents,” The Journal of Cardiovascular Phar macology and Therapeutics, 2013 (in press). doi:10.1177/1074248413492906

  
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