Display options
Share it on

Mol Autism. 2014 Jan 10;5(1):3. doi: 10.1186/2040-2392-5-3.

Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum.

Molecular autism

Catherine Edmonson, Mark N Ziats, Owen M Rennert

Affiliations

  1. Laboratory of Clinical and Developmental Genomics, National Institute of Child Health and Human Development, National Institutes of Health, 49 Convent Drive, Building 49, Room 2C078, Bethesda, MD 20814, USA.
  2. University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32603, USA.
  3. University of Cambridge, Robinson College, Grange Rd, Cambridgeshire CB3 9AN, UK.
  4. Baylor College of Medicine MSTP, One Baylor Plaza, Houston, TX 77030, USA.

PMID: 24410870 PMCID: PMC3914711 DOI: 10.1186/2040-2392-5-3

Abstract

BACKGROUND: The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not completely understood, but ASDs are thought to ultimately result from disrupted synaptogenesis. However, studies have also shown that glial cell numbers and function are abnormal in post-mortem brain tissue from autistic patients. Direct assessment of glial cells in post-mortem human brain tissue is technically challenging, limiting glial research in human ASD studies. Therefore, we attempted to determine if glial cell-type specific markers may be altered in autistic brain tissue in a manner that is consistent with known cellular findings, such that they could serve as a proxy for glial cell numbers and/or activation patterns.

METHODS: We assessed the relative expression of five glial-specific markers and two neuron-specific markers via qRT-PCR. We studied tissue samples from the prefrontal cortex (PFC) and cerebellum of nine post-mortem autistic brain samples and nine neurologically-normal controls. Relative fold-change in gene expression was determined using the ΔΔCt method normalized to housekeeping gene β-actin, with a two-tailed Student's t-test P <0.05 between groups considered as significant.

RESULTS: Both astrocyte- and microglial-specific markers were significantly more highly expressed in autistic PFC as compared to matched controls, while in the cerebellum only astrocyte markers were elevated in autistic samples. In contrast, neuron-specific markers showed significantly lower expression in both the PFC and cerebellum of autistic patients as compared to controls.

CONCLUSIONS: These results are in line with previous findings showing increased glial cell numbers and up-regulation of glial cell gene expression in autistic post-mortem brain tissue, particularly in the PFC, as well as decreased number of neurons in both the PFC and cerebellum of autistic patients. The concordance of these results with cell-level studies in post-mortem autistic brain tissue suggests that expression of glial cell-type specific markers may serve as a useful alternative to traditional cellular characterization methods, especially when appropriately-preserved post-mortem tissue is lacking. Additionally, these results demonstrate abnormal glial-specific gene expression in autistic brains, supporting previous studies that have observed altered glial cell numbers or activation patterns in ASDs. Future work should directly assess the correlation between cell-type specific marker levels and cell number and activation patterns.

References

  1. J Neuroinflammation. 2013 Jul 17;10:85 - PubMed
  2. J Neurosci Res. 2009 Aug 1;87(10):2245-54 - PubMed
  3. Nat Rev Neurol. 2010 Sep;6(9):2 p following 523 - PubMed
  4. Autism Res. 2011 Jun;4(3):200-11 - PubMed
  5. J Clin Invest. 2003 Feb;111(3):323-32 - PubMed
  6. J Mol Neurosci. 2013 Mar;49(3):589-93 - PubMed
  7. Transl Neurodegener. 2013 Aug 08;2(1):17 - PubMed
  8. Biochem Biophys Res Commun. 1996 Jul 25;224(3):855-62 - PubMed
  9. J Comp Neurol. 1994 Mar 1;341(1):95-116 - PubMed
  10. Brain Res. 2012 May 25;1456:72-81 - PubMed
  11. Brain Pathol. 2007 Oct;17(4):422-33 - PubMed
  12. Science. 2011 Sep 9;333(6048):1456-8 - PubMed
  13. J Exp Med. 2005 Feb 21;201(4):647-57 - PubMed
  14. Mol Autism. 2013 Jan 25;4(1):3 - PubMed
  15. Brain. 1998 May;121 ( Pt 5):889-905 - PubMed
  16. Cereb Cortex. 2007 Apr;17(4):951-61 - PubMed
  17. Synapse. 2008 Jul;62(7):501-7 - PubMed
  18. J Neuroimmunol. 2001 Oct 1;119(2):214-22 - PubMed
  19. Dev Neurosci. 1997;19(1):49-57 - PubMed
  20. J Neurosci. 2009 Apr 22;29(16):5051-61 - PubMed
  21. JAMA. 2011 Nov 9;306(18):2001-10 - PubMed
  22. Cerebellum. 2005;4(3):206-10 - PubMed
  23. Oncogene. 2002 Jun 6;21(25):4050-9 - PubMed
  24. J Autism Dev Disord. 2012 Dec;42(12):2569-84 - PubMed
  25. Annu Rev Immunol. 2009;27:119-45 - PubMed
  26. JAMA Psychiatry. 2013 Jan;70(1):49-58 - PubMed
  27. Histochem Cell Biol. 2013 Jul;140(1):13-22 - PubMed
  28. Mol Psychiatry. 2000 Mar;5(2):142-9 - PubMed
  29. MMWR Surveill Summ. 2012 Mar 30;61(3):1-19 - PubMed
  30. Nature. 2011 Jun 29;475(7357):497-500 - PubMed
  31. Nat Neurosci. 2013 Dec;16(12):1896-905 - PubMed
  32. Neuropathology. 2010 Oct;30(5):463-70 - PubMed
  33. Trends Neurosci. 2001 Aug;24(8):450-5 - PubMed
  34. Cerebellum. 2013 Oct;12(5):776-7 - PubMed
  35. Ann Neurol. 2005 Mar;57(3):310-26 - PubMed
  36. Dev Neurobiol. 2012 Oct;72(10):1288-301 - PubMed
  37. N Engl J Med. 2013 Jan 10;368(2):107-16 - PubMed
  38. Neuron. 2007 Oct 25;56(2):399-413 - PubMed
  39. Acta Neurol Scand. 2010 Feb;121(2):99-108 - PubMed
  40. Nature. 2011 Oct 26;478(7370):442-3 - PubMed
  41. Neurology. 2001 Nov 13;57(9):1618-28 - PubMed
  42. Science. 2003 Oct 31;302(5646):826-30 - PubMed
  43. Ann Neurol. 2005 Jan;57(1):67-81 - PubMed
  44. Brain Res. 2011 Mar 22;1380:138-45 - PubMed
  45. Anat Rec (Hoboken). 2011 Oct;294(10):1646-52 - PubMed
  46. Nature. 2012 Mar 18;484(7392):105-9 - PubMed
  47. J Neuroinflammation. 2012 Sep 21;9:223 - PubMed
  48. Biochim Biophys Acta. 2010 Nov;1802(11):1006-12 - PubMed
  49. Front Cell Neurosci. 2013 Mar 18;7:26 - PubMed
  50. Biol Psychiatry. 2010 Aug 15;68(4):368-76 - PubMed
  51. J Neurosci. 2010 Apr 14;30(15):5346-56 - PubMed
  52. Nature. 2010 Nov 11;468(7321):223-31 - PubMed
  53. Hum Immunol. 2013 Jun;74(6):730-7 - PubMed
  54. Mol Autism. 2012 Nov 01;3(1):12 - PubMed
  55. Genes Brain Behav. 2003 Oct;2(5):255-67 - PubMed

Publication Types