Skip to main content
SpringerLink
Log in

Lipid Signalling in the Pathology of Autism Spectrum Disorders

  • Reference work entry
Comprehensive Guide to Autism

Abstract

Autism spectrum disorders (ASDs) result from multifaceted deficits and manifest differently in every individual. The developmental abnormalities of ASDs could be a consequence of genetic aberrations, environmental stressors, or interactions between the two during critical periods of neurodevelopment. Increasing attention has been devoted to investigating lipid signalling molecules since lipids play pivotal roles in the development and function of the human brain and body by acting as regulatory molecules that modulate growth and maintenance. Growing evidence supports the idea that altered fatty acid metabolic pathways may be involved in the pathogenesis of autism and contribute to the variable expression of autism-related traits. This chapter provides an overview of the abnormalities associated with the synthesis of lipid signalling metabolites in individuals with ASDs due to genetic and environmental factors, including dietary lipid imbalances, oxidative stress, and immunological triggers. In particular, the deficits associated with the lipid metabolic pathway for prostaglandin biosynthesis are discussed in further detail. The existing literature provides compelling evidence for the contribution of altered lipid neurobiology to the pathology of ASDs and reveals potential molecular mechanisms that may be important for the development of novel treatments and interventions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,199.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet. 2008;9(5):341–55.

    PubMed  Google Scholar 

  • Abu-Khalil A, Fu L, Grove EA, Zecevic N, Geschwind DH. Wnt genes define distinct boundaries in the developing human brain: implications for human forebrain patterning. J Comp Neurol. 2004;474(2):276–88.

    PubMed  Google Scholar 

  • Adibhatla RM, Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem. 2008;49:241–68.

    PubMed  Google Scholar 

  • Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L. Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009;42(10–11):1032–40.

    PubMed  Google Scholar 

  • Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31(3):137–45.

    PubMed  Google Scholar 

  • Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 2007;61(4):551–3.

    PubMed  Google Scholar 

  • Aneja A, Tierney E. Autism: the role of cholesterol in treatment. Int rev psychiatry (Abingdon, England). 2008;20(2):165–70.

    Google Scholar 

  • Ashwood P, Van de Water J. A review of autism and the immune response. Clin Dev Immunol. 2004;11(2):165–74.

    PubMed  Google Scholar 

  • Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006;80(1):1–15.

    PubMed  Google Scholar 

  • Atladottir HO, Thorsen P, Ostergaard L, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2010;40(12):1423–30.

    PubMed  Google Scholar 

  • Bandim JM, Ventura LO, Miller MT, Almeida HC, Costa AE. Autism and mobius sequence: an exploratory study of children in northeastern Brazil. Arq Neuropsiquiatr. 2003;61(2A):181–5.

    PubMed  Google Scholar 

  • Bell JG, MacKinlay EE, Dick JR, MacDonald DJ, Boyle RM, Glen AC. Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids. 2004;71(4):201–4.

    PubMed  Google Scholar 

  • Bell JG, Miller D, MacDonald DJ, et al. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr. 2010;103(8):1160–7.

    PubMed  Google Scholar 

  • Boland LM, Drzewiecki MM, Timoney G, Casey E. Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels. Am J Physiol Cell Physiol. 2009;296(5):C1003–14.

    PubMed  Google Scholar 

  • Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol. 2001;41:661–90.

    PubMed  Google Scholar 

  • Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010;167(3):261–80.

    PubMed  Google Scholar 

  • Buchanan FG, DuBois RN. Connecting COX-2 and Wnt in cancer. Cancer Cell. 2006;9(1):6–8.

    PubMed  Google Scholar 

  • Buechling T, Boutros M. Wnt signaling signaling at and above the receptor level. Curr Top Dev Biol. 2011;97:21–53.

    PubMed  Google Scholar 

  • Bukelis I, Porter FD, Zimmerman AW, Tierney E. Smith-Lemli-Opitz syndrome and autism spectrum disorder. Am J Psychiatry. 2007;164(11):1655–61.

    PubMed  Google Scholar 

  • Burks SR, Wright CL, McCarthy MM. Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience. 2007;146(3):1117–27.

    PubMed  Google Scholar 

  • Buyske S, Williams TA, Mars AE, et al. Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genet. 2006;7:8.

    PubMed  Google Scholar 

  • Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004;90(4):979–88.

    PubMed  Google Scholar 

  • Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310(5753):1504–10.

    PubMed  Google Scholar 

  • Chauhan A, Chauhan V, Brown WT, Cohen I. Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin – the antioxidant proteins. Life Sci. 2004;75(21):2539–49.

    PubMed  Google Scholar 

  • Choe E. Chemistry and Reactions of Reactive Oxygen Species in Lipid Oxidation. In A. Kamal-Eldin & D. Min (Eds.), Lipid Oxidation Pathways. 2010;2:31–50. Urbana, IL: AOCS Publishing.

    Google Scholar 

  • Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM. Inflammatory processes in preterm and term parturition. J Reprod Immunol. 2008;79(1):50–7.

    PubMed  Google Scholar 

  • Ciani L, Salinas PC. WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci. 2005;6(5):351–62.

    PubMed  Google Scholar 

  • Clandinin MT, Jumpsen J, Suh M. Relationship between fatty acid accretion, membrane composition, and biologic functions. J Pediatr. 1994;125(5 Pt 2):S25–32.

    PubMed  Google Scholar 

  • Craddock N, Lendon C. Chromosome workshop: chromosomes 11, 14, and 15. Am J Med Genet. 1999;88(3):244–54.

    PubMed  Google Scholar 

  • Crawford MA, Hassam AG, Stevens PA. Essential fatty acid requirements in pregnancy and lactation with special reference to brain development. Prog Lipid Res. 1981;20:31–40.

    PubMed  Google Scholar 

  • Crawford MA, Doyle W, Drury P, Lennon A, Costeloe K, Leighfield M. n-6 and n-3 fatty acids during early human development. J Intern Med Suppl. 1989;731:159–69.

    PubMed  Google Scholar 

  • De Felice C, Ciccoli L, Leoncini S, et al. Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med. 2009;47(4):440–8.

    PubMed  Google Scholar 

  • de la Cochetière MF, Rougé C, Darmaun D, Rozé JC, Potel G, Gras-Leguen C. Intestinal microbiota in neonates and preterm infants: a review. Curr Pediatr Rev. 2007;3:21–34.

    Google Scholar 

  • de Vries HE, Blom-Roosemalen MC, van Oosten M, et al. The influence of cytokines on the integrity of the blood–brain barrier in vitro. J Neuroimmunol. 1996;64(1):37–43.

    PubMed  Google Scholar 

  • Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology. 2008;29(1):190–201.

    PubMed  Google Scholar 

  • Dubois A, Rattaz C, Pry R, Baghdadli A. Autism and pain – a literature review. Pain Res Manag. 2010;15(4):245–53.

    PubMed  Google Scholar 

  • Evans T. Fishing for a WNT-PGE2 link: beta-catenin is caught in the stem cell net-work. Cell Stem Cell. 2009;4(4):280–2.

    PubMed  Google Scholar 

  • Evans TA, Siedlak SL, Lu L, et al. The autistic phenotype exhibits a remarkably localized modification of brain protein by products of free radical-induced lipid oxidation. Am J Biotechno Biochem. 2008;4(2):61–72.

    Google Scholar 

  • Farooqui AA, Horrocks LA, Farooqui T. Modulation of inflammation in brain: a matter of fat. J Neurochem. 2007;101(3):577–99.

    PubMed  Google Scholar 

  • Fatemi SH, Halt AR, Realmuto G, et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol. 2002;22(2):171–5.

    PubMed  Google Scholar 

  • Fatemi SH, Pearce DA, Brooks AI, Sidwell RW. Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: a potential animal model for schizophrenia and autism. Synapse. 2005;57(2):91–9.

    PubMed  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD, et al. Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res. 2008;99(1–3):56–70.

    PubMed  Google Scholar 

  • Ferrucci L, Cherubini A, Bandinelli S, et al. Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab. 2006;91(2):439–46.

    PubMed  Google Scholar 

  • Filomeni G, Ciriolo MR. Redox control of apoptosis: an update. Antioxid Redox Signal. 2006;8(11–12):2187–92.

    PubMed  Google Scholar 

  • Fitzgerald DW, Bezak K, Ocheretina O, et al. The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E2 levels. Cancer Prev Res (Phila). 2012;5(1):34–40.

    Google Scholar 

  • Galceran J, Farinas I, Depew MJ, Clevers H, Grosschedl R. Wnt3a-/-- like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13(6):709–17.

    PubMed  Google Scholar 

  • Gaulden J, Reiter JF. Neur-ons and neur-offs: regulators of neural induction in vertebrate embryos and embryonic stem cells. Hum Mol Genet. 2008;17(R1):R60–6.

    PubMed  Google Scholar 

  • Genest DR, Di Salvo D, Rosenblatt MJ, Holmes LB. Terminal transverse limb defects with tethering and omphalocele in a 17 week fetus following first trimester misoprostol exposure. Clin Dysmorphol. 1999;8(1):53–8.

    PubMed  Google Scholar 

  • Genetos DC, Yellowley CE, Loots GG. Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression. PLoS One. 2011;6(3):e17772.

    PubMed  Google Scholar 

  • Ghanizadeh A, Akhondzadeh S, Hormozi, Makarem A, Abotorabi M, Firoozabadi A. Glutathione-related Factors and Oxidative Stress in Autism, a Review. Curr Med Chem. 2012;19(23):4000–5.

    PubMed  Google Scholar 

  • Gilbert SF. Developmental biology. 7th ed. Sunderland: Sinauer Associates; 2003.

    Google Scholar 

  • Goessling W, North TE, Loewer S, et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009;136(6):1136–47.

    PubMed  Google Scholar 

  • Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012;5(2):101–8.

    PubMed  Google Scholar 

  • Gross GA, Imamura T, Luedke C, et al. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Proc Natl Acad Sci USA. 1998;95(20):11875–9.

    PubMed  Google Scholar 

  • Guizy M, David M, Arias C, et al. Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, alpha-linolenic acid. J Mol Cell Cardiol. 2008;44(2):323–35.

    PubMed  Google Scholar 

  • Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003;48(3):195–203.

    PubMed  Google Scholar 

  • Hall AC, Lucas FR, Salinas PC. Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell. 2000;100(5):525–35.

    PubMed  Google Scholar 

  • Harvey L, Boksa P. Prenatal and postnatal animal models of immune activation: Relevance to a range of neurodevelopmental disorders. Dev Neurobiol. Oct 2012;72(10):1335–48.

    PubMed  Google Scholar 

  • Harvey RJ, Depner UB, Wassle H, et al. GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science. 2004;304(5672):884–7.

    PubMed  Google Scholar 

  • Hinz B, Brune K. Cyclooxygenase-2 – 10 years later. J Pharmacol Exp Ther. 2002;300(2):367–75.

    PubMed  Google Scholar 

  • Hoffman DR, Boettcher JA, Diersen-Schade DA. Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2–3):151–8.

    PubMed  Google Scholar 

  • James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004;80(6):1611–7.

    PubMed  Google Scholar 

  • Jiang J, Ganesh T, Du Y, et al. Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor. Proc Natl Acad Sci USA. 2010;107(5):2307–12.

    PubMed  Google Scholar 

  • Johnson SM, Hollander E. Evidence that eicosapentaenoic acid is effective in treating autism. J Clin Psychiatry. 2003;64(7):848–9.

    PubMed  Google Scholar 

  • Jonakait GM, Ni L. Prostaglandins compromise basal forebrain cholinergic neuron differentiation and survival: action at EP1/3 receptors results in AIF-induced death. Brain Res. 2009;1285:30–41.

    PubMed  Google Scholar 

  • Kaufmann WE, Worley PF, Taylor CV, Bremer M, Isakson PC. Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome. Brain Dev. 1997;19(1):25–34.

    PubMed  Google Scholar 

  • Kitase Y, Barragan L, Qing H, et al. Mechanical induction of PGE2 in osteocytes blocks glucocorticoid-induced apoptosis through both the beta-catenin and PKA pathways. J Bone Miner Res. 2010;25(12):2657–68.

    PubMed  Google Scholar 

  • Koch H, Huh SE, Elsen FP, et al. Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures. J Neurosci. 2010;30(35):11678–87.

    PubMed  Google Scholar 

  • Kohane IS, McMurry A, Weber G, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One. 2012;7(4):e33224.

    PubMed  Google Scholar 

  • Krey JF, Dolmetsch RE. Molecular mechanisms of autism: a possible role for Ca2+ signaling. Curr Opin Neurobiol. 2007;17(1):112–9.

    PubMed  Google Scholar 

  • Kwiecien S, Konturek PC, Sliwowski Z, et al. Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress. J Physiol Pharmacol. 2012;63(2):143–51.

    PubMed  Google Scholar 

  • Ladesich JB, Pottala JV, Romaker A, Harris WS. Membrane level of omega-3 docosahexaenoic acid is associated with severity of obstructive sleep apnea. J Clin Sleep Med. 2011;7(4):391–6.

    PubMed  Google Scholar 

  • Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001;40(1–2):1–94.

    PubMed  Google Scholar 

  • Lawrence GD. The fats of life: essential fatty acids in health and disease. New Brunswick: Rutgers University Press; 2010.

    Google Scholar 

  • Legler DF, Bruckner M, Uetz-von Allmen E, Krause P. Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol. 2010;42(2):198–201.

    PubMed  Google Scholar 

  • Lennon PA, Cooper ML, Peiffer DA, et al. Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review. Am J Med Genet A. 2007;143A(8):791–8.

    PubMed  Google Scholar 

  • Libbey JE, Sweeten TL, McMahon WM, Fujinami RS. Autistic disorder and viral infections. J Neurovirol. 2005;11(1):1–10.

    PubMed  Google Scholar 

  • Lin CJ, Chien SC, Chen CP. The use of misoprostol in termination of second-trimester pregnancy. Taiwan J Obstet Gynecol. 2011;50(3):275–82.

    PubMed  Google Scholar 

  • Lin PI, Chien YL, Wu YY, et al. The WNT2 gene polymorphism associated with speech delay inherent to autism. Res Dev Disabil. 2012;33(5):1533–40.

    PubMed  Google Scholar 

  • Liu XH, Kirschenbaum A, Weinstein BM, Zaidi M, Yao S, Levine AC. Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells. Biochem Biophys Res Commun. 2010;394(3):715–20.

    PubMed  Google Scholar 

  • Loftin CD, Tiano HF, Langenbach R. Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 2002;68–69:177–85.

    PubMed  Google Scholar 

  • Ma DQ, Cuccaro ML, Jaworski JM, et al. Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Mol Psychiatry. 2007;12(4):376–84.

    PubMed  Google Scholar 

  • Marin P, Hamon B, Glowinski J, Premont J. Nicotine-induced inhibition of neuronal phospholipase A2. J Pharmacol Exp Ther. 1997;280(3):1277–83.

    PubMed  Google Scholar 

  • Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992;120(4 Pt 2):S129–38.

    PubMed  Google Scholar 

  • Meguid NA, Atta HM, Gouda AS, Khalil RO. Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem. 2008;41(13):1044–8.

    PubMed  Google Scholar 

  • Ming X, Johnson WG, Stenroos ES, Mars A, Lambert GH, Buyske S. Genetic variant of glutathione peroxidase 1 in autism. Brain Dev. 2010;32(2):105–9.

    PubMed  Google Scholar 

  • Morales E, Bustamante M, Gonzalez JR, et al. Genetic variants of the FADS gene cluster and ELOVL gene family, colostrums LC-PUFA levels, breastfeeding, and child cognition. PLoS One. 2011;6(2):e17181.

    PubMed  Google Scholar 

  • Morris CR, Agin MC. Syndrome of allergy, apraxia, and malabsorption: characterization of a neurodevelopmental phenotype that responds to omega 3 and vitamin E supplementation. Altern Ther Health Med. 2009;15(4):34–43.

    PubMed  Google Scholar 

  • Mostafa GA, El-Hadidi ES, Hewedi DH, Abdou MM. Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol. 2010;219(1–2):114–8.

    PubMed  Google Scholar 

  • Murakami M, Kudo I. Phospholipase A2. J Biochem. 2002;131(3):285–92.

    PubMed  Google Scholar 

  • O'Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993;330(2):156–60.

    PubMed  Google Scholar 

  • Ono H, Sakamoto A, Sakura N. Plasma total glutathione concentrations in healthy pediatric and adult subjects. Clin Chim Acta. 2001;312(1–2):227–9.

    PubMed  Google Scholar 

  • Oshima H, Oshima M. Mouse models of gastric tumors: Wnt activation and PGE2 induction. Pathol Int. 2010;60(9):599–607.

    PubMed  Google Scholar 

  • Oshima H, Oguma K, Du YC, Oshima M. Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models. Cancer Sci. 2009;100(10):1779–85.

    PubMed  Google Scholar 

  • Patrick L, Salik R. The effect of essential fatty acid supplementation on language development and learning skills in autism and Asperger’s syndrome. Autism Asperger’s Digest. 2005; Jan–Feb:36–7.

    Google Scholar 

  • Pepicelli O, Fedele E, Berardi M, et al. Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-D-aspartate receptors in rat hippocampus. J Neurochem. 2005;93(6):1561–7.

    PubMed  Google Scholar 

  • Politi P, Cena H, Comelli M, et al. Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study. Arch Med Res. 2008;39(7):682–5.

    PubMed  Google Scholar 

  • Ponzio NM, Servatius R, Beck K, Marzouk A, Kreider T. Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Ann N Y Acad Sci. 2007;1107:118–28.

    PubMed  Google Scholar 

  • Pratico D, Lawson JA, Rokach J, FitzGerald GA. The isoprostanes in biology and medicine. Trends Endocrinol Metab. 2001;12(6):243–7.

    PubMed  Google Scholar 

  • Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000.

    PubMed  Google Scholar 

  • Rice D, Barone Jr S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108 Suppl 3:511–33.

    PubMed  Google Scholar 

  • Rothwell NJ, Hopkins SJ. Cytokines and the nervous system. I: expression and recognition. Trends Neurosci. 1995;18(2):83–8.

    PubMed  Google Scholar 

  • Russo I, Amornphimoltham P, Weigert R, Barlati S, Bosetti F. Cyclooxygenase-1 is involved in the inhibition of hippocampal neurogenesis after lipopolysaccharide-induced neuroinflammation. Cell Cycle. 2011;10(15):2568–73.

    PubMed  Google Scholar 

  • Sahores M, Salinas PC. Activity-mediated synapse formation a role for Wnt-Fz signaling. Curr Top Dev Biol. 2011;97:119–36.

    PubMed  Google Scholar 

  • Saint-Dizier M, Guyader-Joly C, Charpigny G, Grimard B, Humblot P, Ponter AA. Expression of enzymes involved in the synthesis of prostaglandin E2 in bovine in vitro-produced embryos. Zygote. 2011;19(3):277–83.

    PubMed  Google Scholar 

  • Sang N, Chen C. Lipid signaling and synaptic plasticity. Neuroscientist. 2006;12(5):425–34.

    PubMed  Google Scholar 

  • Sastry PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res. 1985;24(2):69–176.

    PubMed  Google Scholar 

  • Schultz ST, Klonoff-Cohen HS, Wingard DL, et al. Breastfeeding, infant formula supplementation, and autistic disorder: the results of a parent survey. Int Breastfeed J. 2006;1:16.

    PubMed  Google Scholar 

  • Sedel F, Bechade C, Vyas S, Triller A. Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death. J Neurosci. 2004;24(9):2236–46.

    PubMed  Google Scholar 

  • Shi L, Fatemi SH, Sidwell RW, Patterson PH. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci. 2003;23(1):297–302.

    PubMed  Google Scholar 

  • Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH. Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun. 2009;23(1):116–23.

    PubMed  Google Scholar 

  • Shukuri M, Takashima-Hirano M, Tokuda K, et al. In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with 11C-ketoprofen methyl ester. J Nucl Med. 2011;52(7):1094–101.

    PubMed  Google Scholar 

  • Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci. 2004;27(8):489–95.

    PubMed  Google Scholar 

  • Shultz SR, Macfabe DF, Martin S, et al. Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. Behav Brain Res. 2009;200(1):33–41.

    PubMed  Google Scholar 

  • Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 1997;82(2):291–5.

    PubMed  Google Scholar 

  • Sikora DM, Pettit-Kekel K, Penfield J, Merkens LS, Steiner RD. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2006;140(14):1511–8.

    PubMed  Google Scholar 

  • Sliwinski S, Croonenberghs J, Christophe A, Deboutte D, Maes M. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism? Neuro Endocrinol Lett. 2006;27(4):465–71.

    PubMed  Google Scholar 

  • Soleymaninejadian E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. Am J Reprod Immunol. 2012;67(1):1–8.

    PubMed  Google Scholar 

  • Stolp H, Neuhaus A, Sundramoorthi R, Molnar Z. The long and the short of it: gene and environment interactions during early cortical development and consequences for long-term neurological disease. Front Psychiatry. 2012;3:50.

    PubMed  Google Scholar 

  • Su HM. Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J Nutr Biochem. 2010;21(5):364–73.

    PubMed  Google Scholar 

  • Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem. 2007;282(16):11613–7.

    PubMed  Google Scholar 

  • Tallberg T, Dabek J, Hallamaa R, Atroshi F. Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component. J lipids. 2011;2011:137175.

    PubMed  Google Scholar 

  • Tamiji J, Crawford DA. Misoprostol elevates intracellular calcium in neuro-2a cells via protein kinase a. Biochem Biophys Res Commun. 2010a;399(4):565–70.

    PubMed  Google Scholar 

  • Tamiji J, Crawford DA. Prostaglandin E(2) and misoprostol induce neurite retraction in neuro-2a cells. Biochem Biophys Res Commun. 2010b;398(3):450–6.

    PubMed  Google Scholar 

  • Tamiji J, Crawford DA. The neurobiology of lipid metabolism in autism spectrum disorders. Neurosignals. 2010c;18(2):98–112.

    PubMed  Google Scholar 

  • Tassoni D, Kaur G, Weisinger RS, Sinclair AJ. The role of eicosanoids in the brain. Asia Pac J Clin Nutr. 2008;17 Suppl 1:220–8.

    PubMed  Google Scholar 

  • Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F, MacFabe DF. Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. J Neurochem. 2010;113(2):515–29.

    PubMed  Google Scholar 

  • Tierney E, Bukelis I, Thompson RE, et al. Abnormalities of cholesterol metabolism in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(6):666–8.

    PubMed  Google Scholar 

  • Vancassel S, Durand G, Barthelemy C, et al. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids. 2001;65(1):1–7.

    PubMed  Google Scholar 

  • Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231(25):232–5.

    PubMed  Google Scholar 

  • Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280–9.

    PubMed  Google Scholar 

  • Wayman GA, Impey S, Marks D, et al. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006;50(6):897–909.

    PubMed  Google Scholar 

  • Wegiel J, Kuchna I, Nowicki K, et al. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol. 2010;119(6):755–70.

    PubMed  Google Scholar 

  • Wiest MM, German JB, Harvey DJ, Watkins SM, Hertz-Picciotto I. Plasma fatty acid profiles in autism: a case–control study. Prostaglandins Leukot Essent Fatty Acids. 2009;80(4):221–7.

    PubMed  Google Scholar 

  • Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet. 1998;352(9129):688–91.

    PubMed  Google Scholar 

  • Williams TA, Mars AE, Buyske SG, et al. Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med. 2007;161(4):356–61.

    PubMed  Google Scholar 

  • Wong C, Li H, Crawford DA. The role of prostaglandin E2 signaling pathway in neuroectodermal stem cell function. Poster# 151.08/V6. Society for Neuroscience – Annual Meeting; Sunday, 13 Nov 2011; 2011. Washington, DC.

    Google Scholar 

  • Wong C, Li H, Crawford DA. The implications of prostaglandin E2-wnt signaling pathway interaction in autism. Poster# 108.128. International meeting for autism research; Thursday, 17 May 2012; 2012, Toronto, Ontario, Canada.

    Google Scholar 

  • Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008;155(3):751–9.

    PubMed  Google Scholar 

  • Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993;11(2):371–86.

    PubMed  Google Scholar 

  • Yao Y, Walsh WJ, McGinnis WR, Pratico D. Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol. 2006;63(8):1161–4.

    PubMed  Google Scholar 

  • Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res. 1999;56(6):565–70.

    PubMed  Google Scholar 

  • Yoo HJ, Cho IH, Park M, et al. Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios. Neurosci Res. 2008;62(1):66–9.

    PubMed  Google Scholar 

  • Zerbo O, Iosif AM, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is Maternal Influenza or Fever During Pregnancy Associated with Autism or Developmental Delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study. J Autism Dev Disord. Jan 2013;43(1):25–33.

    PubMed  Google Scholar 

  • Zhang J, Rivest S. Anti-inflammatory effects of prostaglandin E2 in the central nervous system in response to brain injury and circulating lipopolysaccharide. J Neurochem. 2001;76(3):855–64.

    PubMed  Google Scholar 

  • Zhou CJ, Zhao C, Pleasure SJ. Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities. J Neurosci. 2004;24(1):121–6.

    PubMed  Google Scholar 

  • Zhou CJ, Borello U, Rubenstein JL, Pleasure SJ. Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway. Neuroscience. 2006;142(4):1119–31.

    PubMed  Google Scholar 

  • Zhu Y, Yu T, Zhang XC, Nagasawa T, Wu JY, Rao Y. Role of the chemokine SDF-1 as the meningeal attractant for embryonic cerebellar neurons. Nat Neurosci. 2002;5(8):719–20.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, York University, Faculty of Health, 4700 Keele Street, Bethune College, Room 346, Toronto, ON, Canada

    Dorota Anna Crawford

  2. School of Kinesiology and Health Science, Neuroscience Diploma Program, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, Canada

    Christine Wong

Authors
  1. Christine Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorota Anna Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dorota Anna Crawford .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Wong, C., Crawford, D.A. (2014). Lipid Signalling in the Pathology of Autism Spectrum Disorders. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_68

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_68

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-4787-0

  • Online ISBN: 978-1-4614-4788-7

  • eBook Packages: Behavioral Science

Publish with us

Policies and ethics

Search

Navigation