Display options
Share it on

Front Pediatr. 2017 Mar 15;5:43. doi: 10.3389/fped.2017.00043. eCollection 2017.

Dynamic Akt/mTOR Signaling in Children with Autism Spectrum Disorder.

Frontiers in pediatrics

Charity Onore, Houa Yang, Judy Van de Water, Paul Ashwood

Affiliations

  1. The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
  2. The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, USA.

PMID: 28361047 PMCID: PMC5350147 DOI: 10.3389/fped.2017.00043

Abstract

Autism spectrum disorder (ASD) is a behaviorally defined disorder affecting 1 in 68 children. Currently, there is no known cause for the majority of ASD cases nor are there physiological diagnostic tools or biomarkers to aid behavioral diagnosis. Whole-genome linkage studies, genome-wide association studies, copy number variation screening, and SNP analyses have identified several ASD candidate genes, but which vary greatly among individuals and family clusters, suggesting that a variety of genetic mutations may result in a common pathology or alter a common mechanistic pathway. The Akt/mammalian target of rapamycin (mTOR) pathway is involved in many cellular processes including synaptic plasticity and immune function that can alter neurodevelopment. In this study, we examined the activity of the Akt/mTOR pathway in cells isolated from children with ASD and typically developing controls. We observed higher activity of mTOR, extracellular receptor kinase, and p70S6 kinase and lower activity of glycogen synthase kinase 3 (GSK3)α and tuberin (TSC2) in cells from children with ASD. These data suggest a phosphorylation pattern indicative of higher activity in the Akt/mTOR pathway in children with general/idiopathic ASD and may suggest a common pathological pathway of interest for ASD.

Keywords: T cells; autism; mTOR; phosphorylation; signaling

References

  1. Biol Psychiatry. 2005 Jul 1;58(1):74-7 - PubMed
  2. Ann Neurol. 2007 Sep;62(3):243-50 - PubMed
  3. Front Mol Neurosci. 2012 Feb 15;5:13 - PubMed
  4. J Autism Dev Disord. 2000 Jun;30(3):205-23 - PubMed
  5. J Neurochem. 2008 Mar;104(6):1433-9 - PubMed
  6. J Neuroimmunol. 2008 Nov 15;204(1-2):149-53 - PubMed
  7. Nat Immunol. 2003 Apr;4(4):313-9 - PubMed
  8. Am J Psychiatry. 2004 Mar;161(3):539-46 - PubMed
  9. J Clin Immunol. 2003 Nov;23(6):504-17 - PubMed
  10. Mol Psychiatry. 2002;7(3):311-6 - PubMed
  11. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76 - PubMed
  12. Autism Res. 2008 Jun;1(3):169-78 - PubMed
  13. Cell. 2008 Oct 31;135(3):401-6 - PubMed
  14. Am J Psychiatry. 2003 Sep;160(9):1691-3 - PubMed
  15. Genes Brain Behav. 2012 Apr;11(3):332-41 - PubMed
  16. J Neurosci. 2002 May 1;22(9):3359-65 - PubMed
  17. Brain Behav Immun. 2013 Jul;31:69-75 - PubMed
  18. Neuron. 2006 May 4;50(3):377-88 - PubMed
  19. J Neurosci. 2005 Dec 7;25(49):11288-99 - PubMed
  20. Trends Mol Med. 2011 Feb;17(2):78-87 - PubMed
  21. J Child Neurol. 2004 Sep;19(9):675-9 - PubMed
  22. Int J Alzheimers Dis. 2011;2011:189728 - PubMed
  23. J Child Psychol Psychiatry. 2005 Sep;46(9):963-71 - PubMed
  24. Brain Behav Immun. 2010 Jan;24(1):64-71 - PubMed
  25. Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16834-9 - PubMed
  26. J Neuroimmunol. 1998 May 1;85(1):106-9 - PubMed
  27. Neuron. 2007 Mar 1;53(5):703-17 - PubMed
  28. Nat Rev Genet. 2008 May;9(5):341-55 - PubMed
  29. Curr Top Microbiol Immunol. 2010;346:245-65 - PubMed
  30. J Autism Dev Disord. 1994 Oct;24(5):659-85 - PubMed
  31. J Child Psychol Psychiatry. 1989 May;30(3):405-16 - PubMed
  32. Brain Behav Immun. 2011 Jul;25(5):840-9 - PubMed
  33. Am J Hum Genet. 1991 Nov;49(5):932-8 - PubMed
  34. J Neurosci. 2009 Feb 11;29(6):1773-83 - PubMed
  35. Genes Dev. 2002 Jun 15;16(12 ):1472-87 - PubMed
  36. Hum Mol Genet. 2009 May 15;18(10):1795-804 - PubMed
  37. J Neuroimmunol. 2008 Dec 15;205(1-2):148-54 - PubMed
  38. Immunol Rev. 2009 Mar;228(1):253-72 - PubMed
  39. Pediatrics. 2008 Aug;122(2):e438-45 - PubMed
  40. Nat Neurosci. 2005 Dec;8(12):1727-34 - PubMed
  41. J Neurosci. 2008 Jul 9;28(28):7174-83 - PubMed
  42. J Neurosci. 2010 Jan 13;30(2):694-702 - PubMed
  43. Nat Genet. 2003 May;34(1):27-9 - PubMed
  44. Nature. 1995 Dec 21-28;378(6559):785-9 - PubMed
  45. Brain Behav Immun. 2009 Jan;23(1):124-33 - PubMed
  46. J Neurosci. 2003 May 1;23 (9):3679-88 - PubMed
  47. J Child Psychol Psychiatry. 1994 Jul;35(5):877-900 - PubMed
  48. Nat Neurosci. 2006 Oct;9(10):1221-5 - PubMed
  49. Am J Psychiatry. 2000 Dec;157(12):2043-5 - PubMed
  50. Mol Psychiatry. 2005 Jun;10(6):563-71 - PubMed
  51. Am J Hum Genet. 2007 Dec;81(6):1289-97 - PubMed
  52. Epidemiology. 1990 Jan;1(1):43-6 - PubMed
  53. Immunol Lett. 1990 Sep;25(4):341-5 - PubMed
  54. Psychol Med. 1995 Jan;25(1):63-77 - PubMed
  55. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):412-5 - PubMed
  56. J Neurosci. 2007 May 23;27(21):5546-58 - PubMed
  57. Nature. 2012 Aug 30;488(7413):647-51 - PubMed
  58. J Neuroinflammation. 2008 Nov 21;5:52 - PubMed
  59. Brain Behav Immun. 2012 Mar;26(3):383-92 - PubMed
  60. EMBO J. 1990 Aug;9(8):2431-8 - PubMed
  61. Cell. 1999 Mar 19;96(6):857-68 - PubMed
  62. Am J Psychiatry. 1979 Oct;136(10):1310-2 - PubMed
  63. Brain Res. 2007 Sep 7;1168:112-23 - PubMed
  64. Br J Psychiatry. 1999 Nov;175:444-51 - PubMed
  65. Trends Immunol. 2003 Jul;24(7):358-63 - PubMed
  66. J Am Acad Child Adolesc Psychiatry. 1987 May;26(3):333-5 - PubMed
  67. Ann Neurol. 2002 Sep;52(3):285-96 - PubMed

Publication Types

Grant support