Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder

  • Elisa L. Hill-Yardin
  • Sonja J. McKeown
  • Gaia Novarino
  • Andreas M. GrabruckerEmail author
Part of the Advances in Anatomy, Embryology and Cell Biology book series (ADVSANAT, volume 224)


Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology.


Autism Spectrum Disorder Autism Spectrum Disorder Enteric Nervous System Autism Spectrum Disorder Patient Autism Spectrum Disorder Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



AMG was supported by the Else-Kröner-Fresenius Stiftung (214_A251) and the junior professor programme of the state of Baden-Wuerttemberg and would like to acknowledge networking support by the COST Action TD1304. ELH-Y was supported by a Dyason Fellowship award (University of Melbourne) and a Medicine, Dentistry and Health Sciences Faculty Fellowship (University of Melbourne).


  1. Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA (2011) Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11:22PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W (2013) Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res 151(2):171–180PubMedCrossRefGoogle Scholar
  3. Argyropoulos A, Gilby KL, Hill-Yardin EL (2013) Studying autism in rodent models: reconciling endophenotypes with comorbidities. Front Hum Neurosci 7:417PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ashwood P, Anthony A, Pellicer AA, Torrente F, Walker-Smith JA, Wakefield AJ (2003) Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol 23(6):504–517PubMedCrossRefGoogle Scholar
  5. Babri S, Doosti MH, Salari AA (2014) Strain-dependent effects of prenatal maternal immune activation on anxiety- and depression-like behaviors in offspring. Brain Behav Immun 37:164–176PubMedCrossRefGoogle Scholar
  6. Baharnoori M, Bhardwaj SK, Srivastava LK (2012) Neonatal behavioral changes in rats with gestational exposure to lipopolysaccharide: a prenatal infection model for developmental neuropsychiatric disorders. Schizophr Bull 38(3):444–456PubMedCrossRefGoogle Scholar
  7. Barbaro J, Dissanayake C (2010) Prospective identification of autism spectrum disorders in infancy and toddlerhood using developmental surveillance: the social attention and communication study. J Dev Behav Pediatr 31(5):376–385PubMedCrossRefGoogle Scholar
  8. Baron MK, Boeckers TM, Vaida B, Faham S, Gingery M, Sawaya M, Salyer D, Gundelfinger ED, Bowie JU (2006) An architectural framework that may lie at the core of the post-synaptic density. Science 311:531–535PubMedCrossRefGoogle Scholar
  9. Berger BE, Navar-Boggan AM, Omer SB (2011) Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination—United States, 2001–2010. BMC Public Health 11:340PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP, Penn O, Witherspoon K, Gerdts J, Baker C, Vulto-van Silfhout AT, Schuurs-Hoeijmakers JH, Fichera M, Bosco P, Buono S, Alberti A, Failla P, Peeters H, Steyaert J, Vissers LE, Francescatto L, Mefford HC, Rosenfeld JA, Bakken T, O’Roak BJ, Pawlus M, Moon R, Shendure J, Amaral DG, Lein E, Rankin J, Romano C, de Vries BB, Katsanis N, Eichler EE (2014) Disruptive CHD8 mutations define a subtype of autism early in development. Cell 158(2):263–276PubMedPubMedCentralCrossRefGoogle Scholar
  11. Besedovsky HO, del Rey A (2011) Central and peripheral cytokines mediate immune-brain connectivity. Neurochem Res 36(1):1–6PubMedCrossRefGoogle Scholar
  12. Besser L, Chorin E, Sekler I, Silverman WF, Atkin S, Russell JT, Hershfinkel M (2009) Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J Neurosci 29(9):2890–2901PubMedPubMedCentralCrossRefGoogle Scholar
  13. Betancur C (2011) Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res 1380:42–77PubMedCrossRefGoogle Scholar
  14. Betancur C, Sakurai T, Buxbaum JD (2009) The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci 32(7):402–412PubMedCrossRefGoogle Scholar
  15. Bienenstock J, Kunze W, Forsythe P (2015) Microbiota and the gut-brain axis. Nutr Rev 73(Suppl 1):28–31PubMedCrossRefGoogle Scholar
  16. Bjorklund G (2013) The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp (Wars) 73(2):225–236Google Scholar
  17. Bohórquez DV, Liddle RA (2015) The gut connectome: making sense of what you eat. J Clin Invest 125(3):888–890PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bohórquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y, Calakos N, Wang F, Liddle RA (2015) Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest 125(2):782–786PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bravo JA, Julio-Pieper M, Forsythe P, Kunze W, Dinan TG, Bienenstock J, Cryan JF (2012) Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol 12(6):667–672PubMedCrossRefGoogle Scholar
  20. Buie T, Campbell DB, Fuchs GJ, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H (2010) Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125(Suppl 1):1–18CrossRefGoogle Scholar
  21. Burns AJ, Roberts RR, Bornstein JC, Young HM (2009) Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Semin Pediatr Surg 18(4):196–205PubMedCrossRefGoogle Scholar
  22. Burrows EL, Laskaris L, Koyama L, Churilov L, Bornstein JC, Hill-Yardin EL, Hannan AJ (2015) A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice. Mol Autism 6:62PubMedPubMedCentralCrossRefGoogle Scholar
  23. Careaga M, Schwartzer J, Ashwood P (2015) Inflammatory profiles in the BTBR mouse: how relevant are they to autism spectrum disorders? Brain Behav Immun 43:11–16PubMedCrossRefGoogle Scholar
  24. Castellan Baldan L, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, Anderson GM, Loring E, Gorczyca R, Billingslea E, Wasylink S, Panza KE, Ercan-Sencicek AG, Krusong K, Leventhal BL, Ohtsu H, Bloch MH, Hughes ZA, Krystal JH, Mayes L, de Araujo I, Ding YS, State MW, Pittenger C (2014) Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron 81(1):77–90PubMedCrossRefGoogle Scholar
  25. Celestino-Soper PB, Violante S, Crawford EL, Luo R, Lionel AC, Delaby E, Cai G, Sadikovic B, Lee K, Lo C, Gao K, Person RE, Moss TJ, German JR, Huang N, Shinawi M, Treadwell-Deering D, Szatmari P, Roberts W, Fernandez B, Schroer RJ, Stevenson RE, Buxbaum JD, Betancur C, Scherer SW, Sanders SJ, Geschwind DH, Sutcliffe JS, Hurles ME, Wanders RJ, Shaw CA, Leal SM, Cook EH, Goin-Kochel RP, Vaz FM, Beaudet AL (2012) A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Proc Natl Acad Sci USA 109(21):7974–7981PubMedPubMedCentralCrossRefGoogle Scholar
  26. Chadman KK, Gong S, Scattoni ML, Boltuck SE, Gandhy SU, Heintz N, Crawley JN (2008) Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res 1(3):147–158PubMedPubMedCentralCrossRefGoogle Scholar
  27. Christianson AL, Chesler N, Kromberg JG (1994) Fetal valproate syndrome: clinical and neuro-developmental features in two sibling pairs. Dev Med Child Neurol 36(4):361–369PubMedCrossRefGoogle Scholar
  28. Coussons-Read ME, Okun ML, Schmitt MP, Giese S (2005) Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy. Psychosom Med 67(4):625–631PubMedCrossRefGoogle Scholar
  29. Cox LM, Cho I, Young SA, Anderson WH, Waters BJ, Hung SC, Gao Z, Mahana D, Bihan M, Alekseyenko AV, Methé BA, Blaser MJ (2013) The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates intestinal microbiota. FASEB J 27(2):692–702PubMedPubMedCentralCrossRefGoogle Scholar
  30. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci 13(10):701–712PubMedCrossRefGoogle Scholar
  31. Cryan JF, Dinan TG (2015) More than a gut feeling: the microbiota regulates neurodevelopment and behavior. Neuropsychopharmacology 40(1):241–242PubMedCrossRefGoogle Scholar
  32. D’Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O (1996) Abnormal intestinal permeability in children with autism. Acta Paediatr 85(9):1076–1079PubMedCrossRefGoogle Scholar
  33. D’Mello C, Ronaghan N, Zaheer R, Dicay M, Le T, MacNaughton WK, Surrette MG, Swain MG (2015) Probiotics improve inflammation-associated sickness behavior by altering communication between the peripheral immune system and the brain. J Neurosci 35(30):10821–10830PubMedCrossRefGoogle Scholar
  34. Damasceno DC, Sinzato YK, Bueno A, Netto AO, Dallaqua B, Gallego FQ, Iessi IL, Corvino SB, Serrano RG, Marini G, Piculo F, Calderon IM, Rudge MV (2013) Mild diabetes models and their maternal-fetal repercussions. J Diabetes Res 2013:473575PubMedPubMedCentralCrossRefGoogle Scholar
  35. De Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M (2015) Autism spectrum disorders and intestinal microbiota. Gut Microbes 6(3):207–213PubMedPubMedCentralCrossRefGoogle Scholar
  36. de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C (2010) Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr 51(4):418–424PubMedCrossRefGoogle Scholar
  37. de Theije CG, Koelink PJ, Korte-Bouws GA, Lopes da Silva S, Korte SM, Olivier B, Garssen J, Kraneveld AD (2014) Intestinal inflammation in a murine model of autism spectrum disorders. Brain Behav Immun 37:240–247PubMedCrossRefGoogle Scholar
  38. Delorme R, Ey E, Toro R, Leboyer M, Gillberg C, Bourgeron T (2013) Progress toward treatments for synaptic defects in autism. Nat Med 19(6):685–694PubMedCrossRefGoogle Scholar
  39. Ehninger D, Sano Y, de Vries PJ, Dies K, Franz D, Geschwind DH, Kaur M, Lee YS, Li W, Lowe JK, Nakagawa JA, Sahin M, Smith K, Whittemore V, Silva AJ (2012) Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry 17(1):62–70PubMedCrossRefGoogle Scholar
  40. Ellis M, Taher AM, McKeown S, Hill EL, Bornstein JC (2012) TU1992 the neuroligin 3 Arg451cys (NL-3) mouse model of autism shows altered colonic function in vitro. Gastroenterology 142(5):895CrossRefGoogle Scholar
  41. Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermöhlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18(7):965–977PubMedCrossRefGoogle Scholar
  42. Etherton M, Földy C, Sharma M, Tabuchi K, Liu X, Shamloo M, Malenka RC, Südhof TC (2011) Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci USA 108(33):13764–13769PubMedPubMedCentralCrossRefGoogle Scholar
  43. Faber S, Zinn GM, Kern JC, Kingston HM (2009) The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers 14(3):171–180PubMedCrossRefGoogle Scholar
  44. Faridar A, Jones-Davis D, Rider E, Li J, Gobius I, Morcom L, Richards LJ, Sen S, Sherr EH (2014) Mapk/Erk activation in an animal model of social deficits shows a possible link to autism. Mol Autism 5:57PubMedPubMedCentralCrossRefGoogle Scholar
  45. Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D, Liu M, Molitoris DR, Green JA (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16(4):444–453PubMedCrossRefGoogle Scholar
  46. Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35(1):6–16CrossRefGoogle Scholar
  47. Forsythe P, Bienenstock J, Kunze WA (2014) Vagal pathways for microbiome-brain-gut axis communication. Adv Exp Med Biol 817:115–133PubMedCrossRefGoogle Scholar
  48. Frederickson CJ, Moncrieff DW (1994) Zinc-containing neurons. Biol Signals 3(3):127–139PubMedCrossRefGoogle Scholar
  49. Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson MA, Davies SE, Berelowitz M, Forbes A, Wakefield AJ, Walker-Smith JA, Murch SH (2001) Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr 138(3):366–372PubMedCrossRefGoogle Scholar
  50. Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9(5):286–294PubMedCrossRefGoogle Scholar
  51. Furness JB, Callaghan BP, Rivera LR, Cho HJ (2014) The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol 817:39–71PubMedCrossRefGoogle Scholar
  52. Galvão MC, Chaves-Kirsten GP, Queiroz-Hazarbassanov N, Carvalho VM, Bernardi MM, Kirsten TB (2015) Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation. Life Sci 120:54–60PubMedCrossRefGoogle Scholar
  53. Gao Y, Liu L, Li Q, Wang Y (2015) Differential alterations in the morphology and electrophysiology of layer II pyramidal cells in the primary visual cortex of a mouse model prenatally exposed to LPS. Neurosci Lett 591:138–143PubMedCrossRefGoogle Scholar
  54. García-Cazorla A, Oyarzabal A, Fort J, Robles C, Castejón E, Ruiz-Sala P, Bodoy S, Merinero B, Lopez-Sala A, Dopazo J, Nunes V, Ugarte M, Artuch R, Palacín M, Rodríguez-Pombo P, Alcaide P, Navarrete R, Sanz P, Font-Llitjós M, Vilaseca MA, Ormaizabal A, Pristoupilova A, Agulló SB (2014) Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients. Hum Mutat 35(4):470–477PubMedCrossRefGoogle Scholar
  55. Gershon MD, Ratcliffe EM (2004) Developmental biology of the enteric nervous system: pathogenesis of Hirschsprung’s disease and other congenital dysmotilities. Semin Pediatr Surg 13(4):224–235PubMedPubMedCentralCrossRefGoogle Scholar
  56. Ghaziuddin M, Al-Owain M (2013) Autism spectrum disorders and inborn errors of metabolism: an update. Pediatr Neurol 49(4):232–236PubMedCrossRefGoogle Scholar
  57. Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P (2012) Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res 5(2):101–108PubMedPubMedCentralCrossRefGoogle Scholar
  58. Grabrucker AM (2012) Environmental factors in autism. Front Psych 3:118Google Scholar
  59. Grabrucker AM (2014) A role for synaptic zinc in ProSAP/Shank PSD scaffold malformation in autism spectrum disorders. Dev Neurobiol 74(2):136–146PubMedCrossRefGoogle Scholar
  60. Grabrucker AM, Schmeisser MJ, Schoen M, Boeckers TM (2011) Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies. Trends Cell Biol 21(10):594–603PubMedCrossRefGoogle Scholar
  61. Grabrucker S, Jannetti L, Eckert M, Gaub S, Chhabra R, Pfaender S, Mangus K, Reddy PP, Rankovic V, Schmeisser MJ, Kreutz MR, Ehret G, Boeckers TM, Grabrucker AM (2014) Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain 137(Pt 1):137–152PubMedCrossRefGoogle Scholar
  62. Grabrucker S, Boeckers TM, Grabrucker AM (2016) Gender dependent evaluation of autism like behavior in mice exposed to prenatal zinc deficiency. Front Behav Neurosci 10:37PubMedPubMedCentralCrossRefGoogle Scholar
  63. Gundelfinger ED, Boeckers TM, Baron M, Bowie JU (2006) A role for zinc in synapse asSAMbly and plasticity? TIBS 31(7):366–373PubMedGoogle Scholar
  64. Gupta S, Ellis SE, Ashar FN, Moes A, Bader JS, Zhan J, West AB, Arking DE (2014) Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun 5:5748PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hagmeyer S, Haderspeck JC, Grabrucker AM (2014) Behavioral impairments in animal models for zinc deficiency. Front Behav Neurosci 8:443PubMedGoogle Scholar
  66. Hamilton PJ, Shekar A, Belovich AN, Christianson NB, Campbell NG, Sutcliffe JS, Galli A, Matthies HJ, Erreger K (2015) Zn(2+) reverses functional deficits in a de novo dopamine transporter variant associated with autism spectrum disorder. Mol Autism 6:8PubMedPubMedCentralCrossRefGoogle Scholar
  67. Hao MM, Bornstein JC, Vanden Berghe P, Lomax AE, Young HM, Foong JP (2013) The emergence of neural activity and its role in the development of the enteric nervous system. Dev Biol 382(1):365–374PubMedCrossRefGoogle Scholar
  68. Haroon E, Raison CL, Miller AH (2012) Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology 37(1):137–162PubMedCrossRefGoogle Scholar
  69. Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132(3):344–362PubMedCrossRefGoogle Scholar
  70. Horvath K, Perman JA (2002) Autism and gastrointestinal symptoms. Curr Gastroenterol Rep 4(3):251–258PubMedCrossRefGoogle Scholar
  71. Hsiao EY (2014) Gastrointestinal issues in autism spectrum disorder. Harv Rev Psychiatry 22(2):104–111PubMedCrossRefGoogle Scholar
  72. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155(7):1451–1463PubMedPubMedCentralCrossRefGoogle Scholar
  73. Hurley LS, Gowan J, Swenerton H (1971) Teratogenic effects of short-term and transitory zinc deficiency in rats. Teratology 4(2):199–204CrossRefGoogle Scholar
  74. Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ (2009) Incidence of gastrointestinal symptoms in children with autism: a population-based study. Pediatrics 124(2):680–686PubMedPubMedCentralCrossRefGoogle Scholar
  75. Iwata K, Matsuzaki H, Takei N, Manabe T, Mori N (2010) Animal models of autism: an epigenetic and environmental viewpoint. J Cent Nerv Syst Dis 2:37–44PubMedPubMedCentralCrossRefGoogle Scholar
  76. Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29PubMedPubMedCentralCrossRefGoogle Scholar
  77. Jan HH, Chen IT, Tsai YY, Chang YC (2002) Structural role of zinc ions bound to postsynaptic densities. J Neurochem 83(3):525–534PubMedCrossRefGoogle Scholar
  78. Jones W, Klin A (2013) Attention to eyes is present but in decline in 2-6-month-old infants later diagnosed with autism. Nature 504(7480):427–431PubMedPubMedCentralCrossRefGoogle Scholar
  79. Joshi MA, Jeoung NH, Obayashi M, Hattab EM, Brocken EG, Liechty EA, Kubek MJ, Vattem KM, Wek RC, Harris RA (2006) Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice. Biochem J 400(1):153–162PubMedPubMedCentralCrossRefGoogle Scholar
  80. Kashyap PC, Marcobal A, Ursell LK, Larauche M, Duboc H, Earle KA, Sonnenburg ED, Ferreyra JA, Higginbottom SK, Million M, Tache Y, Pasricha PJ, Knight R, Farrugia G, Sonnenburg JL (2013) Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology 144(5):967–977PubMedPubMedCentralCrossRefGoogle Scholar
  81. Khoshdel A, Verdu EF, Kunze W, McLean P, Bergonzelli G, Huizinga JD (2013) Bifidobacterium longum NCC3001 inhibits AH neuron excitability. Neurogastroenterol Motil 25(7):e478–e484PubMedCrossRefGoogle Scholar
  82. Kirsten TB, Chaves-Kirsten GP, Chaible LM, Silva AC, Martins DO, Britto LR, Dagli ML, Torrão AS, Palermo-Neto J, Bernardi MM (2012) Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide. J Neurosci Res 90(10):1903–1912PubMedCrossRefGoogle Scholar
  83. Kirsten TB, Chaves-Kirsten GP, Bernardes S, Scavone C, Sarkis JE, Bernardi MM, Felicio LF (2015a) Lipopolysaccharide exposure induces maternal hypozincemia, and prenatal zinc treatment prevents autistic-like behaviors and disturbances in the striatal dopaminergic and mTOR systems of offspring. PLoS One 10(7):e0134565PubMedPubMedCentralCrossRefGoogle Scholar
  84. Kirsten TB, Queiroz-Hazarbassanov N, Bernardi MM, Felicio LF (2015b) Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure. Life Sci 130:12–17PubMedCrossRefGoogle Scholar
  85. Koh JY, Lim JS, Byun HR, Yoo MH (2014) Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients. Mol Brain 7:64PubMedPubMedCentralCrossRefGoogle Scholar
  86. Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L, Kunkel L, Bickel J, Wattanasin N, Spence S, Murphy S, Churchill S (2012) The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One 7(4):e33224PubMedPubMedCentralCrossRefGoogle Scholar
  87. Koo SI, Turk DE (1977) Effect of zinc deficiency on the ultrastructure of the pancreatic acinar cell and intestinal epithelium in the rat. J Nutr 107(5):896–908PubMedGoogle Scholar
  88. Koumura A, Kakefuda K, Honda A, Ito Y, Tsuruma K, Shimazawa M, Uchida Y, Hozumi I, Satoh M, Inuzuka T, Hara H (2009) Metallothionein-3 deficient mice exhibit abnormalities of psychological behaviors. Neurosci Lett 467(1):11–14PubMedCrossRefGoogle Scholar
  89. Kunze WA, Mao YK, Wang B, Huizinga JD, Ma X, Forsythe P, Bienenstock J (2009) Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J Cell Mol Med 13(8B):2261–2270PubMedCrossRefGoogle Scholar
  90. Landa RJ (2008) Diagnosis of autism spectrum disorders in the first 3 years of life. Nat Clin Pract Neurol 4(3):138–147PubMedCrossRefGoogle Scholar
  91. Le Belle JE, Sperry J, Ngo A, Ghochani Y, Laks DR, López-Aranda M, Silva AJ, Kornblum HI (2014) Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells. Stem Cell Rep 3(5):725–734CrossRefGoogle Scholar
  92. Lee EJ, Choi SY, Kim E (2015a) NMDA receptor dysfunction in autism spectrum disorders. Curr Opin Pharmacol 20:8–13PubMedCrossRefGoogle Scholar
  93. Lee EJ, Lee H, Huang TN, Chung C, Shin W, Kim K, Koh JY, Hsueh YP, Kim E (2015b) Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation. Nat Commun 6:7168PubMedPubMedCentralCrossRefGoogle Scholar
  94. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, Buja A, Krieger A, Yoon S, Troge J, Rodgers L, Iossifov I, Wigler M (2011) Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70(5):886–897PubMedCrossRefGoogle Scholar
  95. Li SO, Wang JL, Bjørklund G, Zhao WN, Yin CH (2014) Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport 25(15):1216–1220PubMedCrossRefGoogle Scholar
  96. Libbey JE, Sweeten TL, McMahon WM, Fujinami RS (2005) Autistic disorder and viral infections. J Neurovirol 11(1):1–10PubMedCrossRefGoogle Scholar
  97. Libermann TA, Baltimore D (1990) Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol 10(5):2327–2334PubMedPubMedCentralCrossRefGoogle Scholar
  98. Liu MJ, Bao S, Gálvez-Peralta M, Pyle CJ, Rudawsky AC, Pavlovicz RE, Killilea DW, Li C, Nebert DW, Wewers MD, Knoell DL (2013) ZIP8 regulates host defense through zinc-mediated inhibition of NF-κB. Cell Rep 3(2):386–400PubMedPubMedCentralCrossRefGoogle Scholar
  99. Lomax AE, Mawe GM, Sharkey KA (2005) Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea-pig. J Physiol 564(Pt 3):863–875PubMedPubMedCentralCrossRefGoogle Scholar
  100. Lu YM, Taverna FA, Tu R, Ackerley CA, Wang YT, Roder J (2000) Endogenous Zn(2+) is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses. Synapse 38(2):187–197PubMedCrossRefGoogle Scholar
  101. Lucchina L, Depino AM (2014) Altered peripheral and central inflammatory responses in a mouse model of autism. Autism Res 7(2):273–289PubMedCrossRefGoogle Scholar
  102. Lundgren O, Jodal M, Jansson M, Ryberg AT, Svensson L (2011) Intestinal epithelial stem/progenitor cells are controlled by mucosal afferent nerves. PLoS One 6(2):e16295PubMedPubMedCentralCrossRefGoogle Scholar
  103. Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH (2012) Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun 26(4):607–616PubMedPubMedCentralCrossRefGoogle Scholar
  104. Mao YK, Kasper DL, Wang B, Forsythe P, Bienenstock J, Kunze WA (2013) Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat Commun 4:1465PubMedCrossRefGoogle Scholar
  105. Marques AH, Bjørke-Monsen AL, Teixeira AL, Silverman MN (2014) Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology. Brain Res 1617:28–46PubMedCrossRefGoogle Scholar
  106. Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20(4):440–446PubMedCrossRefGoogle Scholar
  107. Mayer EA, Padua D, Tillisch K (2014) Altered brain-gut axis in autism: comorbidity or causative mechanisms? Bioessays 36(10):933–939PubMedCrossRefGoogle Scholar
  108. Mazur-Kolecka B, Cohen IL, Gonzalez M, Jenkins EC, Kaczmarski W, Brown WT, Flory M, Frackowiak J (2014) Autoantibodies against neuronal progenitors in sera from children with autism. Brain Dev 36(4):322–329PubMedCrossRefGoogle Scholar
  109. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN (2008) Autism-like behavioral phenotypes in BTBR T + tf/J mice. Genes Brain Behav 7(2):152–163PubMedCrossRefGoogle Scholar
  110. McVey Neufeld KA, Perez-Burgos A, Mao YK, Bienenstock J, Kunze WA (2015) The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin. Neurogastroenterol Motil 27(5):627–636PubMedCrossRefGoogle Scholar
  111. Meyer U (2014) Prenatal poly(i:C) exposure and other developmental immune activation models in rodent systems. Biol Psychiatry 75(4):307–315PubMedCrossRefGoogle Scholar
  112. Mueller BR, Bale TL (2007) Early prenatal stress impact on coping strategies and learning performance is sex dependent. Physiol Behav 91(1):55–65PubMedCrossRefGoogle Scholar
  113. Muller PA, Koscsó B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, Mortha A, Leboeuf M, Li XM, Mucida D, Stanley ER, Dahan S, Margolis KG, Gershon MD, Merad M, Bogunovic M (2014) Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158(2):300–313PubMedPubMedCentralCrossRefGoogle Scholar
  114. Novarino G, El-Fishawy P, Kayserili H, Meguid NA, Scott EM, Schroth J, Silhavy JL, Kara M, Khalil RO, Ben-Omran T, Ercan-Sencicek AG, Hashish AF, Sanders SJ, Gupta AR, Hashem HS, Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris RA, State MW, Gleeson JG (2012) Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science 338(6105):394–397PubMedPubMedCentralCrossRefGoogle Scholar
  115. Nuttall JR, Oteiza PI (2012) Zinc and the ERK kinases in the developing brain. Neurotox Res 21(1):128–141PubMedCrossRefGoogle Scholar
  116. O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res 277:32–48PubMedCrossRefGoogle Scholar
  117. O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE (2011) Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet 43(6):585–589PubMedPubMedCentralCrossRefGoogle Scholar
  118. Parracho HM, Bingham MO, Gibson GR, McCartney AL (2005) Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 54(Pt 10):987–991PubMedCrossRefGoogle Scholar
  119. Peters S, Koh J, Choi DW (1987) Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. Science 236(4801):589–593PubMedCrossRefGoogle Scholar
  120. Pfaender S, Grabrucker AM (2014) Characterization of biometal profiles in neurological disorders. Metallomics 6(5):960–977PubMedCrossRefGoogle Scholar
  121. Pfeiffer CC, Braverman ER (1982) Zinc, the brain and behavior. Biol Psychiatry 17(4):513–532PubMedGoogle Scholar
  122. Pletnikov MV, Moran TH, Carbone KM (2002) Borna disease virus infection of the neonatal rat: developmental brain injury model of autism spectrum disorders. Front Biosci 7:d593–d607PubMedGoogle Scholar
  123. Prado EL, Dewey KG (2014) Nutrition and brain development in early life. Nutr Rev 72(4):267–284PubMedCrossRefGoogle Scholar
  124. Prasad AS, Bao B, Beck FW, Sarkar FH (2011) Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB. Nutrition 27(7–8):816–823PubMedCrossRefGoogle Scholar
  125. Quarterman J, Jackson FA, Morrison JN (1976) The effect of zinc deficiency on sheep intestinal mucin. Life Sci 19(7):979–986PubMedCrossRefGoogle Scholar
  126. Raab M, Boeckers TM, Neuhuber WL (2010) Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3)-scaffolding proteins are also present in postsynaptic specializations of the peripheral nervous system. Neuroscience 171(2):421–433PubMedCrossRefGoogle Scholar
  127. Ratcliffe EM, Farrar NR, Fox EA (2011) Development of the vagal innervation of the gut: steering the wandering nerve. Neurogastroenterol Motil 23(10):898–911PubMedPubMedCentralCrossRefGoogle Scholar
  128. Rossi CC, Van de Water J, Rogers SJ, Amaral DG (2011) Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders. Brain Behav Immun 25(6):1123–1135PubMedPubMedCentralCrossRefGoogle Scholar
  129. Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O, Lim BK, Fowler SC, Malenka RC, Südhof TC (2014) Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell 158(1):198–212PubMedPubMedCentralCrossRefGoogle Scholar
  130. Russo AJ, Bazin AP, Bigega R, Carlson RS, Cole MG, Contreras DC, Galvin MB, Gaydorus SS, Holik SD, Jenkins GP, Jones BM, Languell PA, Lyman PJ, March KP, Meuer KA, Peterson SR, Piedmonte MT, Quinn MG, Smaranda NC, Steves PL, Taylor HP, Waddingham TE, Warren JS (2012) Plasma copper and zinc concentration in individuals with autism correlate with selected symptom severity. Nutr Metab Insights 5:41–47PubMedPubMedCentralCrossRefGoogle Scholar
  131. Samuelsson AM, Jennische E, Hansson HA, Holmäng A (2006) Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. Am J Physiol Regul Integr Comp Physiol 290(5):R1345–R1356PubMedCrossRefGoogle Scholar
  132. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Günel M, Roeder K, Geschwind DH, Devlin B, State MW (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485(7397):237–241PubMedPubMedCentralCrossRefGoogle Scholar
  133. Sauder C, de la Torre JC (1999) Cytokine expression in the rat central nervous system following perinatal Borna disease virus infection. J Neuroimmunol 96(1):29–45PubMedCrossRefGoogle Scholar
  134. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74(4):691–705PubMedPubMedCentralCrossRefGoogle Scholar
  135. Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH (2013) The influence of diet on the gut microbiota. Pharmacol Res 69(1):52–60PubMedCrossRefGoogle Scholar
  136. Seifi M, Brown JF, Mills J, Bhandari P, Belelli D, Lambert JJ, Rudolph U, Swinny JD (2014) Molecular and functional diversity of GABA-A receptors in the enteric nervous system of the mouse colon. J Neurosci 34(31):10361–10378PubMedPubMedCentralCrossRefGoogle Scholar
  137. Sensi SL, Canzoniero LM, Yu SP, Ying HS, Koh JY, Kerchner GA, Choi DW (1997) Measurement of intracellular free zinc in living cortical neurons: routes of entry. J Neurosci 17(24):9554–9564PubMedGoogle Scholar
  138. Serajee FJ, Nabi R, Zhong H, Huq M (2004) Polymorphisms in xenobiotic metabolism genes and autism. J Child Neurol 19(6):413–417PubMedGoogle Scholar
  139. Sharkey KA, Savidge TC (2014) Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract. Auton Neurosci 181:94–106PubMedCrossRefGoogle Scholar
  140. Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23(1):297–302PubMedGoogle Scholar
  141. Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27(40):10695–10702PubMedPubMedCentralCrossRefGoogle Scholar
  142. Song Y, Liu C, Finegold SM (2004) Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 70(11):6459–6465PubMedPubMedCentralCrossRefGoogle Scholar
  143. Southon S, Gee JM, Johnson IT (1984) Hexose transport and mucosal morphology in the small intestine of the zinc-deficient rat. Br J Nutr 52(2):371–380PubMedCrossRefGoogle Scholar
  144. Southon S, Livesey G, Gee JM, Johnson IT (1985) Intestinal cellular proliferation and protein synthesis in zinc-deficient rats. Br J Nutr 53(3):595–603PubMedCrossRefGoogle Scholar
  145. Szuran TF, Pliska V, Pokorny J, Welzl H (2000) Prenatal stress in rats: effects on plasma corticosterone, hippocampal glucocorticoid receptors, and maze performance. Physiol Behav 71(3–4):353–362PubMedCrossRefGoogle Scholar
  146. Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Südhof TC (2007) A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318(5847):71–76PubMedPubMedCentralCrossRefGoogle Scholar
  147. Theoharides TC, Stewart JM, Panagiotidou S, Melamed I (2015a) Mast cells, brain inflammation and autism. Eur J Pharmacol 778:96–102PubMedCrossRefGoogle Scholar
  148. Theoharides TC, Athanassiou M, Panagiotidou S, Doyle R (2015b) Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders. J Neuroimmunol 279:33–38PubMedCrossRefGoogle Scholar
  149. Torrente F, Ashwood P, Day R, Machado N, Furlano RI, Anthony A, Davies SE, Wakefield AJ, Thomson MA, Walker-Smith JA, Murch SH (2002) Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry 7(4):375–382, 334Google Scholar
  150. Torrente F, Anthony A, Heuschkel RB, Thomson MA, Ashwood P, Murch SH (2004) Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s and Helicobacter pylori gastritis. Am J Gastroenterol 99(4):598–605PubMedCrossRefGoogle Scholar
  151. Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S (2006) Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr 27(2 Suppl):128–136CrossRefGoogle Scholar
  152. Van Lieshout RJ, Voruganti LP (2008) Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms. J Psychiatry Neurosci 33(5):395–404PubMedPubMedCentralGoogle Scholar
  153. Vela G, Stark P, Socha M, Sauer AK, Hagmeyer S, Grabrucker AM (2015) Zinc in gut-brain interaction in autism and neurological disorders. Neural Plast 2015:972791PubMedPubMedCentralCrossRefGoogle Scholar
  154. Voineagu I, Eapen V (2013) Converging pathways in autism spectrum disorders: interplay between synaptic dysfunction and immune responses. Front Hum Neurosci 7:738PubMedPubMedCentralCrossRefGoogle Scholar
  155. Wallace AS, Burns AJ (2005) Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract. Cell Tissue Res 319(3):367–382PubMedCrossRefGoogle Scholar
  156. Wang LW, Tancredi DJ, Thomas DW (2011) The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr 32(5):351–360PubMedCrossRefGoogle Scholar
  157. Warkany J, Petering HG (1972) Congenital malformations of the central nervous system in rats produced by maternal zinc deficiency. Teratology 5(3):319–334PubMedCrossRefGoogle Scholar
  158. Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, Li X (2011) IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 8:52PubMedPubMedCentralCrossRefGoogle Scholar
  159. Wessells KR, Brown KH (2012) Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One 7(11):e50568PubMedPubMedCentralCrossRefGoogle Scholar
  160. Westbrook GL, Mayer ML (1987) Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 328(6131):640–643PubMedCrossRefGoogle Scholar
  161. Wojtkiewicz J, Gonkowski S, Równiak M, Crayton R, Majewski M, Jałyński M (2012a) Neurochemical characterization of zinc transporter 3-like immunoreactive (ZnT3(+)) neurons in the intramural ganglia of the porcine duodenum. J Mol Neurosci 48(3):766–776PubMedPubMedCentralCrossRefGoogle Scholar
  162. Wojtkiewicz J, Równiak M, Crayton R, Majewski M, Gonkowski S (2012b) Chemical coding of zinc-enriched neurons in the intramural ganglia of the porcine jejunum. Cell Tissue Res 350(2):215–223PubMedPubMedCentralCrossRefGoogle Scholar
  163. Xie X, Smart TG (1994) Modulation of long-term potentiation in rat hippocampal pyramidal neurons by zinc. Pflugers Arch 427(5–6):481–486PubMedCrossRefGoogle Scholar
  164. Xuan IC, Hampson DR (2014) Gender-dependent effects of maternal immune activation on the behavior of mouse offspring. PLoS One 9(8):e104433PubMedPubMedCentralCrossRefGoogle Scholar
  165. Yasuda H, Yoshida K, Yasuda Y, Tsutsui T (2011) Infantile zinc deficiency: association with autism spectrum disorders. Sci Rep 1:129PubMedPubMedCentralCrossRefGoogle Scholar
  166. Yoo MH, Kim TY, Yoon YH, Koh JY (2016) Autism phenotypes in ZnT3 null mice: involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation. Sci Rep 6:28548PubMedPubMedCentralCrossRefGoogle Scholar
  167. Zhang Q, Wang J, Li A, Liu H, Zhang W, Cui X, Wang K (2013) Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease. Mol Biol Rep 40(4):2969–2975PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Elisa L. Hill-Yardin
    • 1
    • 2
  • Sonja J. McKeown
    • 3
    • 4
  • Gaia Novarino
    • 5
  • Andreas M. Grabrucker
    • 6
    • 7
    Email author
  1. 1.Department of PhysiologyUniversity of MelbourneMelbourneAustralia
  2. 2.School of Health and Biomedical SciencesRMIT UniversityMelbourneAustralia
  3. 3.Department of Anatomy and NeuroscienceUniversity of MelbourneMelbourneAustralia
  4. 4.Department of Anatomy and Developmental BiologyMonash UniversityClaytonAustralia
  5. 5.Institute of Science and Technology AustriaKlosterneuburgAustria
  6. 6.WG Molecular Analysis of Synaptopathies, Department of NeurologyNeurocenter of Ulm UniversityUlmGermany
  7. 7.Department of Biological SciencesUniversity of LimerickLimerickIreland

Personalised recommendations