Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice

Journal of Neuroscience Research

Volumn 91, Issue 9, 2013, Pages 1143-1151

  Crain, Jessica M ^a   Nikodemova, Maria ^b   Watters, Jyoti J ^a,b  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Aging; Development; M1 M2 phenotype; Microglia; Sexual dimorphism

Indexed keywords

ARGINASE 1; CD11B ANTIGEN; ESTROGEN RECEPTOR; FC RECEPTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; MESSENGER RNA; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ADULTHOOD; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DOWN REGULATION; FEMALE; FLOW CYTOMETRY; GENOTYPE; IMMUNOCOMPETENT CELL; MALE; MICROGLIA; NONHUMAN; ONTOGENY; PERINATAL PERIOD; PHENOTYPE; POSTNATAL DEVELOPMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; SEX DIFFERENCE;

AGING; DEVELOPMENT; M1/M2 PHENOTYPE; MICROGLIA; SEXUAL DIMORPHISM;

AGE FACTORS; ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; CENTRAL NERVOUS SYSTEM; CYTOKINES; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENOTYPE; MALE; MICE; MICE, INBRED C57BL; MICROGLIA; NERVE TISSUE PROTEINS; PHENOTYPE; RNA, MESSENGER; SEX CHARACTERISTICS; TRANSCRIPTOME;

EID: 84880513276     PISSN: 03604012     EISSN: 10974547     Source Type: Journal    
DOI: 10.1002/jnr.23242     Document Type: Article

References (50)

1. Arevalo MA, Diz-Chaves Y, Santos-Galindo M, Bellini MJ, Garcia-Segura LM. 2012. Selective oestrogen receptor modulators decrease the inflammatory response of glial cells. J Neuroendocrinol 24:183-190.
2. Baker AE, Brautigam VM, Watters JJ. 2004. Estrogen modulates microglial inflammatory mediator production via interactions with estrogen receptor beta. Endocrinology 145:5021-5032.
3. Balthazart J, Ball GF. 1998. New insights into the regulation and function of brain estrogen synthase (aromatase). Trends Neurosci 21:243-249.
4. Bansal V, Ochoa JB. 2003. Arginine availability, arginase, and the immune response. Curr Opin Clin Nutr Metab are 6:223-228.
5. Bloch GJ, Kurth SM, Akesson TR, Micevych PE. 1992. Estrogen-concentrating cells within cell groups of the medial preoptic area: sex differences and colocalization with galanin-immunoreactive cells. Brain Res 595:301-308.
6. Brown CM, Xu Q, Okhubo N, Vitek MP, Colton CA. 2007. Androgen-mediated immune function is altered by the apolipoprotein E gene. Endocrinology 148:3383-3390.
7. Chang CI, Liao JC, Kuo L. 1998. Arginase modulates nitric oxide production in activated macrophages. Am J Physiol 274:H342-H348.
8. Conde JR, Streit WJ. 2006. Microglia in the aging brain. J Neuropathol Exp Neurol 65:199-203.
9. Crain JM, Nikodemova M, Watters JJ. 2009. Expression of P2 nucleotide receptors varies with age and sex in murine brain microglia. J Neuroinflammation 6:24.
10. Cribbs DH, Berchtold NC, Perreau V, Coleman PD, Rogers J, Tenner AJ, Cotman CW. 2012. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. J Neuroinflam 9:179.
11. Flores CA, Shughrue P, Petersen SL, Mokha SS. 2003. Sex-related differences in the distribution of opioid receptor-like 1 receptor mRNA and colocalization with estrogen receptor mRNA in neurons of the spinal trigeminal nucleus caudalis in the rat. Neuroscience 118:769-778.
12. Foo LC, Allen NJ, Bushong EA, Ventura PB, Chung WS, Zhou L, Cahoy JD, Daneman R, Zong H, Ellisman MH, Barres BA. 2011. Development of a method for the purification and culture of rodent astrocytes. Neuron 71:799-811.
13. Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, Johnson RW. 2005. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 19:1329-1331.
14. Graeber MB. 2010. Changing face of microglia. Science 330:783-788.
15. Graeber MB, Li W, Rodriguez ML. 2011. Role of microglia in CNS inflammation. FEBS Lett 585:3798-3805.
16. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD. 2000. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:1768-1771.
17. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. 2011. Physiology of microglia. Physiol Rev 91:461-553.
18. Lewis DK, Johnson AB, Stohlgren S, Harms A, Sohrabji F. 2008. Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats. J Neuroimmunol 195:47-59.
19. Lira A, Kulczycki J, Slack R, Anisman H, Park DS. 2011. Involvement of the Fc gamma receptor in a chronic N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of dopaminergic loss. J Biol Chem 286:28783-28793.
20. Liu M, Yin Y, Ye X, Zeng M, Zhao Q, Keefe DL, Liu L. 2013. Resveratrol protects against age-associated infertility in mice. Hum Reprod (in press).
21. Logroscino G, Traynor BJ, Hardiman O, Chio A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E. 2010. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81:385-390.
22. Lunnon K, Teeling JL, Tutt AL, Cragg MS, Glennie MJ, Perry VH. 2011. Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J Immunol 186:7215-7224.
23. McCoy MK, Tansey MG. 2008. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflam 5:45.
24. Mor G, Nilsen J, Horvath T, Bechmann I, Brown S, Garcia-Segura LM, Naftolin F. 1999. Estrogen and microglia: a regulatory system that affects the brain. J Neurobiol 40:484-496.
25. Mori M. 2007. Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. J Nutr 137(Suppl 2):1616S-1620S.
26. Nikodemova M, Watters JJ. 2012. Efficient isolation of live microglia with preserved phenotypes from adult mouse brain. J Neuroinflam 9:147.
27. Nikodemova M, Watters JJ, Jackson SJ, Yang SK, Duncan ID. 2007. Minocycline down-regulates MHC II expression in microglia and macrophages through inhibition of IRF-1 and protein kinase C (PKC)alpha/betaII. J Biol Chem 282:15208-15216.
28. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT. 2011. Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456-1458.
29. Parkhurst CN, Gan WB. 2010. Microglia dynamics and function in the CNS. Curr Opin Neurobiol 20:595-600.
30. Payami H, Zareparsi S, Montee KR, Sexton GJ, Kaye JA, Bird TD, Yu CE, Wijsman EM, Heston LL, Litt M, Schellenberg GD. 1996. Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet 58:803-811.
31. Sato T, Matsumoto T, Kawano H, Watanabe T, Uematsu Y, Sekine K, Fukuda T, Aihara K, Krust A, Yamada T, Nakamichi Y, Yamamoto Y, Nakamura T, Yoshimura K, Yoshizawa T, Metzger D, Chambon P, Kato S. 2004. Brain masculinization requires androgen receptor function. Proc Natl Acad Sci U S A 101:1673-1678.
32. Schwarz JM, Sholar PW, Bilbo SD. 2012. Sex differences in microglial colonization of the developing rat brain. J Neurochem 120:948-963.
33. Shughrue PJ, Dellovade TL, Merchenthaler I. 2002. Estrogen modulates oxytocin gene expression in regions of the rat supraoptic and paraventricular nuclei that contain estrogen receptor-beta. Prog Brain Res 139:15-29.
34. Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K. 2007. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 55:412-424.
35. Sierra A, Gottfried-Blackmore A, Milner TA, McEwen BS, Bulloch K. 2008. Steroid hormone receptor expression and function in microglia. Glia 56:659-674.
36. Simerly RB, Zee MC, Pendleton JW, Lubahn DB, Korach KS. 1997. Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse. Proc Natl Acad Sci U S A 94:14077-14082.
37. Smith JA, Das A, Butler JT, Ray SK, Banik NL. 2011. Estrogen or estrogen receptor agonist inhibits lipopolysaccharide induced microglial activation and death. Neurochem Res 36:1587-1593.
38. Spence RD, Hamby ME, Umeda E, Itoh N, Du S, Wisdom AJ, Cao Y, Bondar G, Lam J, Ao Y, Sandoval F, Suriany S, Sofroniew MV, Voskuhl RR. 2011. Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc Natl Acad Sci U S A 108:8867-8872.
39. Streit WJ, Conde JR, Fendrick SE, Flanary BE, Mariani CL. 2005. Role of microglia in the central nervous system's immune response. Neurol Res 27:685-691.
40. Takahashi N, Tonchev AB, Koike K, Murakami K, Yamada K, Yamashima T, Inoue M. 2004. Expression of estrogen receptor-beta in the postischemic monkey hippocampus. Neurosci Lett 369:9-13.
41. Tremblay ME, Majewska AK. 2011. A role for microglia in synaptic plasticity? Commun Integr Biol 4:220-222.
42. Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. 2011. The role of microglia in the healthy brain. J Neurosci 31:16064-16069.
43. Vegeto E, Belcredito S, Ghisletti S, Meda C, Etteri S, Maggi A. 2006. The endogenous estrogen status regulates microglia reactivity in animal models of neuroinflammation. Endocrinology 147:2263-2272.
44. Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, Cellai I, Maneschi E, Serni S, Gacci M, Carini M, Piccinni MP, Saad F, Adorini L, Vannelli GB, Maggi M. 2012. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol 212:71-84.
45. von Bernhardi R, Tichauer JE, Eugenin J. 2010. Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. J Neurochem 112:1099-1114.
46. Voskuhl RR, Gold SM. 2012. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol 8:255-263.
47. Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J. 2009. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974-3980.
48. Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. 2011. Epidemiology and etiology of Parkinson's disease: a review of the evidence. Eur J Epidemiol 26(Suppl 1):S1-S58.
49. Witham EA, Meadows JD, Shojaei S, Kauffman AS, Mellon PL. 2012. Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice. Endocrinology (in press).
50. Zhou L, Zhu DY. 2009. Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide Biol Chem 20:223-230.