title: Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function.
abstract: Traditionally, microglia have been considered to act as macrophages of the central nervous system. While this concept still remains true it is also becoming increasingly apparent that microglia are involved in a host of nonimmunological activities, such as monitoring synaptic function and maintaining synaptic integrity. It has also become apparent that microglia are exquisitely sensitive to perturbation by environmental challenges. The aim of the current review is to critically examine the now substantial literature that has developed around the ability of acute, sub-chronic and chronic stressors to alter microglial structure and function. The vast majority of studies have demonstrated that stress promotes significant structural remodelling of microglia, and can enhance the release of pro-inflammatory cytokines from microglia. Mechanistically, many of these effects appear to be driven by traditional stress-linked signalling molecules, namely corticosterone and norepinephrine. The specific effects of these signalling molecules are, however, complex as they can exert both inhibitory and suppressive effects on microglia depending upon the duration and intensity of exposure. Importantly, research has now shown that these stress-induced microglial alterations, rather than being epiphenomena, have broader behavioural implications, with the available evidence implicating microglia in directly regulating certain aspects of cognitive function and emotional regulation.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia. Walker@newcastle.edu.au.
authors.forename: Frederick Rohan
authors.initials: FR
authors.lastname: Walker
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: Kimberley
authors.initials: K
authors.lastname: Jones
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000503:physiopathology; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D017628:Microglia / Q000502:physiology*; D019964:Mood Disorders / Q000503:physiopathology; D009473:Neuronal Plasticity; D010641:Phenotype; D013315:Stress, Psychological / Q000503:physiopathology*
references.citation: Cereb Cortex. 2013 Aug;23(8):1784-97
references.pmid: 22710611
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1195-200
references.pmid: 16213079
references.citation: J Pharmacol Exp Ther. 2003 Jan;304(1):1-7
references.pmid: 12490568
references.citation: J Neuroinflammation. 2004 Jun 30;1(1):9
references.pmid: 15285793
references.citation: Science. 2013 Mar 1;339(6123):1095-9
references.pmid: 23449593
references.citation: Neuroscience. 2005;135(4):1295-307
references.pmid: 16165282
references.citation: Cytokine. 2003 Dec 21;24(6):254-65
references.pmid: 14609567
references.citation: Exp Neurol. 2007 Jul;206(1):33-42
references.pmid: 17481608
references.citation: Cereb Cortex. 2012 Jun;22(6):1442-54
references.pmid: 21878486
references.citation: Neuroscience. 2013 Mar 1;232:13-20
references.pmid: 23262242
references.citation: Nat Rev Neurosci. 2009 Jun;10(6):397-409
references.pmid: 19469025
references.citation: J Neurochem. 2002 Nov;83(4):754-63
references.pmid: 12421347
references.citation: Neuroscience. 2006 May 12;139(2):475-83
references.pmid: 16473474
references.citation: Brain Behav Immun. 2010 May;24(4):660-71
references.pmid: 20193756
references.citation: Blood. 1993 Mar 15;81(6):1607-13
references.pmid: 7680921
references.citation: Psychoneuroendocrinology. 2012 Sep;37(9):1491-505
references.pmid: 22386198
references.citation: Behav Brain Res. 2012 May 16;231(1):130-7
references.pmid: 22465167
references.citation: Brain Behav Immun. 2007 Jan;21(1):47-59
references.pmid: 16647243
references.citation: Trends Neurosci. 1996 Aug;19(8):312-8
references.pmid: 8843599
references.citation: Glia. 1994 May;11(1):18-34
references.pmid: 8070892
references.citation: Neuroscience. 1999;91(4):1277-89
references.pmid: 10391435
references.citation: Brain Res. 2000 Dec 15;886(1-2):172-189
references.pmid: 11119695
references.citation: J Neuroinflammation. 2004 Jul 30;1(1):14
references.pmid: 15285801
references.citation: Brain Behav Immun. 2010 Jan;24(1):19-30
references.pmid: 19647070
references.citation: J Infect Dis. 1992 Oct;166(4):847-53
references.pmid: 1527422
references.citation: Br Med Bull. 1996 Jul;52(3):597-617
references.pmid: 8949260
references.citation: J Neurosci. 2004 Dec 15;24(50):11439-48
references.pmid: 15601950
references.citation: Neurosci Res. 2006 Apr;54(4):319-27
references.pmid: 16473422
references.citation: Brain Behav Immun. 2013 Oct;33:1-6
references.pmid: 23459026
references.citation: Sci Signal. 2009 Jun 16;2(75):ra28
references.pmid: 19531803
references.citation: Brain Res. 2009 Oct 13;1293:108-13
references.pmid: 19361488
references.citation: Neuroscience. 1990;39(1):151-70
references.pmid: 2089275
references.citation: Glia. 1997 May;20(1):23-37
references.pmid: 9145302
references.citation: J Neurosci. 2009 Apr 1;29(13):3974-80
references.pmid: 19339593
references.citation: Prog Neurobiol. 1999 Apr;57(6):563-81
references.pmid: 10221782
references.citation: Neuropsychopharmacology. 2000 Oct;23(4):428-38
references.pmid: 10989270
references.citation: Brain Behav Immun. 2009 Aug;23(6):851-60
references.pmid: 19361551
references.citation: J Neuroimmunol. 2006 Feb;171(1-2):72-85
references.pmid: 16278020
references.citation: J Neurosci. 2011 Nov 9;31(45):16064-9
references.pmid: 22072657
references.citation: J Neuroimmune Pharmacol. 2012 Mar;7(1):266-78
references.pmid: 22249489
references.citation: Acta Neuropathol. 2013 Jul;126(1):75-91
references.pmid: 23512378
references.citation: J Neurosci. 2001 Apr 15;21(8):2580-8
references.pmid: 11306611
references.citation: Immunol Cell Biol. 2006 Dec;84(6):551-6
references.pmid: 16956390
references.citation: Int J Neuropsychopharmacol. 2009 Jun;12(5):687-99
references.pmid: 19046481
references.citation: J Neuroimmunol. 2011 Apr;233(1-2):29-36
references.pmid: 21115202
references.citation: Brain Behav Immun. 2013 Mar;29:136-146
references.pmid: 23305936
references.citation: Neurobiol Aging. 2011 Jan;32(1):85-102
references.pmid: 19286276
references.citation: Nature. 2011 Apr 21;472(7343):319-24
references.pmid: 21389984
references.citation: Curr Immunol Rev. 2010 Aug 1;6(3):195-204
references.pmid: 20729991
references.citation: Physiol Rev. 2011 Apr;91(2):461-553
references.pmid: 21527731
references.citation: Neuropharmacology. 2008 Oct;55(5):826-34
references.pmid: 18639562
references.citation: J Neuroimmunol. 1989 Feb;21(2-3):117-23
references.pmid: 2913044
references.citation: Neurosci Biobehav Rev. 2011 Apr;35(5):1291-301
references.pmid: 21316391
references.citation: Acta Neuropathol. 2003 Dec;106(6):518-26
references.pmid: 14513261
references.citation: J Neuroimmunol. 2006 Apr;173(1-2):87-95
references.pmid: 16386803
references.citation: Brain Behav Immun. 2002 Aug;16(4):461-76
references.pmid: 12096891
references.citation: Neuropharmacology. 2002 Nov;43(6):1026-34
references.pmid: 12423672
references.citation: Brain Behav Immun. 2012 Feb;26(2):337-45
references.pmid: 22041296
references.citation: Mol Cell Neurosci. 2005 May;29(1):128-38
references.pmid: 15866053
references.citation: J Neurosci. 2006 Feb 8;26(6):1880-7
references.pmid: 16467537
references.citation: Brain Behav Immun. 2012 Mar;26(3):469-79
references.pmid: 22251606
references.citation: Gastroenterology. 2009 Apr;136(4):1339-48, e1-2
references.pmid: 19249394
references.citation: Brain Res Bull. 1994;34(1):73-8
references.pmid: 8193937
references.citation: Physiol Behav. 2013 Oct 2;122:246-52
references.pmid: 23707717
references.citation: Acta Neuropathol. 2010 Jan;119(1):89-105
references.pmid: 20012873
references.citation: Brain Res. 2010 May 6;1329:45-54
references.pmid: 20230803
references.citation: J Neurosci. 2006 May 24;26(21):5709-19
references.pmid: 16723527
references.citation: Glia. 2001 Mar 1;33(3):256-66
references.pmid: 11241743
references.citation: PLoS One. 2011 Jan 25;6(1):e15973
references.pmid: 21283568
references.citation: Neuroscience. 2007 May 25;146(3):1388-99
references.pmid: 17433555
references.citation: Glia. 2008 Apr 15;56(6):659-74
references.pmid: 18286612
references.citation: Brain Behav Immun. 2009 Oct;23(7):958-68
references.pmid: 19464360
references.citation: Glia. 2008 Aug 1;56(10):1114-26
references.pmid: 18442093
references.citation: Neuropsychopharmacology. 2005 Aug;30(8):1576-83
references.pmid: 15886723
references.citation: Acta Neuropathol. 2001 Mar;101(3):249-55
references.pmid: 11307625
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1201-13
references.pmid: 16271821
references.citation: Brain Res Bull. 2012 Aug 1;88(5):471-6
references.pmid: 22537595
references.citation: PLoS Biol. 2010 Nov 02;8(11):e1000527
references.pmid: 21072242
references.citation: Nat Neurosci. 2005 Jun;8(6):752-8
references.pmid: 15895084
references.citation: Stress. 2007 Nov;10(4):311-3; discussion 314-5
references.pmid: 17999347
references.citation: J Neurosci. 2011 Apr 27;31(17):6277-88
references.pmid: 21525267
references.citation: Annu Rev Clin Psychol. 2005;1:293-319
references.pmid: 17716090
references.citation: Brain Behav Immun. 2010 Oct;24(7):1058-68
references.pmid: 20153418
references.citation: Cell Signal. 2007 Feb;19(2):251-60
references.pmid: 16996249
references.citation: Neurochem Int. 1996 Jul;29(1):43-53
references.pmid: 8808788
references.citation: Neurochem Res. 2011 May;36(5):701-12
references.pmid: 21207139
references.citation: Neuroscience. 2012 Dec 6;225:162-71
references.pmid: 22824429
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15983-8
references.pmid: 14668448
references.citation: Eur J Neurosci. 2006 Jan;23(1):83-93
references.pmid: 16420418
references.citation: J Neuroimmunol. 2009 Feb 15;207(1-2):24-31
references.pmid: 19111355
references.citation: Neuropsychopharmacology. 2006 Aug;31(8):1616-26
references.pmid: 16395301
references.citation: J Neurosci. 2002 Aug 1;22(15):6810-8
references.pmid: 12151561
references.citation: Trends Neurosci. 1997 Feb;20(2):78-84
references.pmid: 9023876
references.citation: Mol Cell Neurosci. 2006 Jan;31(1):149-60
references.pmid: 16297637
references.citation: Science. 2005 May 27;308(5726):1314-8
references.pmid: 15831717
references.citation: J Neuroimmunol. 2013 Jan 15;254(1-2):161-4
references.pmid: 22944319
references.citation: Acta Neuropathol. 2007 Jun;113(6):675-82
references.pmid: 17265048