Display options
Share it on

eNeuro. 2015 Aug 31;2(4). doi: 10.1523/ENEURO.0036-15.2015. eCollection 2015.

Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum.

eNeuro

Miguel Perez-Pouchoulen, Jonathan W VanRyzin, Margaret M McCarthy

Affiliations

  1. Department of Pharmacology, University of Maryland School of Medicine , Baltimore, Maryland 21201.
  2. Department of Pharmacology, University of Maryland School of Medicine , Baltimore, Maryland 21201 ; Program in Neuroscience, University of Maryland School of Medicine , Baltimore, Maryland 21201.

PMID: 26464992 PMCID: PMC4596010 DOI: 10.1523/ENEURO.0036-15.2015

Abstract

Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from P17 to P19, with an approximately fourfold increase compared with the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (ML; ∼31%) during a 3 d window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At P17 males showed an approximately twofold increase in microglia with thin processes compared with females. Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.

Keywords: cell death; development; microglia; phagocytosis; sex difference; vermis

References

  1. J Neurol. 2003 Sep;250(9):1025-36 - PubMed
  2. Trends Neurosci. 2012 Nov;35(11):700-9 - PubMed
  3. Nat Rev Neurosci. 2012 May 18;13(6):395-406 - PubMed
  4. Front Cell Neurosci. 2013 Jan 30;7:6 - PubMed
  5. Trends Neurosci. 1998 Sep;21(9):375-82 - PubMed
  6. Curr Opin Neurol. 2013 Apr;26(2):146-53 - PubMed
  7. J Neurosci. 2011 Oct 26;31(43):15511-21 - PubMed
  8. Brain Res Rev. 2010 Oct 5;65(1):14-27 - PubMed
  9. Brain Struct Funct. 2014 Jan;219(1):151-70 - PubMed
  10. Addict Biol. 2014 May;19(3):317-31 - PubMed
  11. Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9 - PubMed
  12. J Comp Neurol. 1997 Dec 22;389(3):390-401 - PubMed
  13. Science. 2011 Sep 9;333(6048):1456-8 - PubMed
  14. Trends Neurosci. 1998 Sep;21(9):370-5 - PubMed
  15. J Neurosci. 2003 Oct 8;23 (27):9185-93 - PubMed
  16. Eur J Neurosci. 1992;4(9):798-812 - PubMed
  17. Neuroscience. 2002;112(3):509-23 - PubMed
  18. Anat Embryol (Berl). 1977 Oct 7;151(2):201-18 - PubMed
  19. Rom J Morphol Embryol. 2013;54(3):467-72 - PubMed
  20. Curr Biol. 2000 Jul 13;10(14):857-60 - PubMed
  21. Neuron. 1993 Oct;11(4):621-32 - PubMed
  22. Neuron. 2004 Feb 19;41(4):535-47 - PubMed
  23. Int J Dev Neurosci. 2001 Feb;19(1):53-62 - PubMed
  24. Neuroscience. 2009 Sep 1;162(3):549-59 - PubMed
  25. J Physiol. 2005 Sep 15;567(Pt 3):829-50 - PubMed
  26. Prog Neurobiol. 2004 Apr;72(5):295-339 - PubMed
  27. PLoS Biol. 2010 Nov 02;8(11):e1000527 - PubMed
  28. Nat Rev Neurosci. 2009 Sep;10(9):670-81 - PubMed
  29. Annu Rev Immunol. 2009;27:119-45 - PubMed
  30. Neuropsychologia. 2003;41(11):1452-60 - PubMed
  31. Annu Rev Cell Dev Biol. 2007;23:549-77 - PubMed
  32. J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):193-8 - PubMed
  33. Curr Drug Abuse Rev. 2009 Jan;2(1):26-40 - PubMed
  34. Acta Neuropathol. 2010 Mar;119(3):303-15 - PubMed
  35. Science. 2005 May 27;308(5726):1314-8 - PubMed
  36. Cell Stem Cell. 2010 Oct 8;7(4):483-95 - PubMed
  37. Neuroscientist. 2008 Feb;14(1):91-100 - PubMed
  38. Neuron. 2012 May 24;74(4):691-705 - PubMed
  39. J Neurochem. 2012 Mar;120(6):948-63 - PubMed
  40. Brain Res Brain Res Rev. 2003 Apr;42(1):85-95 - PubMed
  41. Cortex. 2010 Jul-Aug;46(7):858-68 - PubMed
  42. Curr Opin Neurobiol. 1992 Dec;2(6):802-6 - PubMed
  43. Neurosci Res. 2005 Nov;53(3):221-8 - PubMed
  44. Cell Death Differ. 2015 Apr;22(4):526-39 - PubMed
  45. Int J Dev Neurosci. 2005 Apr-May;23(2-3):183-7 - PubMed
  46. Ann Neurol. 2005 Jan;57(1):67-81 - PubMed
  47. Nat Rev Mol Cell Biol. 2008 Aug;9(8):639-49 - PubMed
  48. Environ Health Perspect. 1975 Dec;12:119-23 - PubMed
  49. J Anat. 1992 Dec;181 ( Pt 3):423-30 - PubMed
  50. Annu Rev Immunol. 2014;32:367-402 - PubMed
  51. J Comp Neurol. 2004 Aug 16;476(2):154-73 - PubMed
  52. Annu Rev Neurosci. 2009;32:413-34 - PubMed
  53. Brain Res. 1988 Jan-Mar;472(1):77-101 - PubMed
  54. J Neurosci. 2003 Aug 27;23(21):7759-66 - PubMed
  55. Cortex. 2010 Jul-Aug;46(7):896-906 - PubMed
  56. J Neurosci. 2013 Feb 13;33(7):2761-72 - PubMed
  57. Brain. 2009 Feb;132(Pt 2):288-95 - PubMed
  58. Nat Rev Neurosci. 2005 Apr;6(4):297-311 - PubMed
  59. Prog Neurobiol. 2003 Aug;70(6):473-507 - PubMed
  60. Brain Res Dev Brain Res. 1990 Sep 1;55(2):219-30 - PubMed
  61. J Comp Neurol. 1972 Aug;145(4):399-463 - PubMed
  62. J Comp Neurol. 1988 Oct 1;276(1):132-56 - PubMed
  63. Development. 2014 Nov;141(21):4031-41 - PubMed
  64. J Neuroendocrinol. 2009 Jun;21(6):519-25 - PubMed
  65. Neurochem Res. 2009 Dec;34(12 ):2078-88 - PubMed
  66. Cerebellum. 2012 Jun;11(2):416-7 - PubMed
  67. J Neurosci. 2011 Nov 9;31(45):16064-9 - PubMed
  68. J Comp Neurol. 1995 Oct 30;361(4):602-16 - PubMed
  69. Trends Neurosci. 2008 Mar;31(3):137-45 - PubMed
  70. Dev Psychobiol. 1981 Jul;14(4):327-32 - PubMed
  71. Cerebellum. 2008;7(1):38-47 - PubMed

Publication Types