Expression of P2 nucleotide receptors varies with age and sex in murine brain microglia.
Microglia are implicated in multiple neurodegenerative disorders, many of which display sexual dimorphisms and have symptom onsets at different ages. P2 purinergic receptors are critical for regulating various microglial functions, but little is known about how their expression varies with age or sex. Therefore, comprehensive information about purinergic receptor expression in normal microglia, in both sexes, over age is necessary if we are to better understand their roles in the healthy and diseased CNS. We analyzed the expression of all fourteen rodent P2X and P2Y receptors in CD11b+ cells freshly-isolated from the brains of C57Bl/6 mice at five different ages ranging from postnatal day 3 to 12 months, in males and females, using quantitative RT-PCR. We also compared purinergic receptor expression in microglia freshly-isolated from 3 day-old pups to that in primary neonatal microglial cultures created from mice of the same age. We observed patterns in P2 receptor expression with age, most notably increased expression with age and age-restricted expression. There were also several receptors that showed sexually dimorphic expression. Lastly, we noted that in vitro culturing of neonatal microglia greatly changed their P2 receptor expression profiles. These data represent the first complete and systematic report of changes in purinergic receptor expression of microglia with age and sex, and provide important information necessary for accurate in vitro modeling of healthy animals.
Crain
Jessica M
JM
Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA. jmcrain@wisc.edu
Nikodemova
Maria
M
Watters
Jyoti J
JJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004660:Encephalitis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12; D012727:Sex Characteristics
C548577:P2ry12 protein, mouse; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12
Glia. 2007 Apr 15;55(6):604-16
17299767
Brain Res. 2003 Aug 15;981(1-2):174-83
12885439
Pharmacol Rev. 2006 Sep;58(3):281-341
16968944
J Neuroimmunol. 2005 Sep;166(1-2):113-25
15979729
Brain Res Brain Res Rev. 2005 Apr;48(2):234-9
15850662
Nature. 2005 Dec 15;438(7070):1017-21
16355225
Nat Neurosci. 2005 Jun;8(6):752-8
15895084
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7438-42
1651506
Brain Res Dev Brain Res. 2005 May 12;156(2):147-57
16099301
Neurol Res. 2005 Oct;27(7):685-91
16197805
Toxicol Pathol. 2000 Jan-Feb;28(1):28-30
10668987
J Comp Neurol. 2008 Jan 1;506(1):75-92
17990272
BMC Neurol. 2006 Mar 02;6:12
16512913
Cell Mol Life Sci. 2007 Jun;64(12):1471-83
17375261
Eur J Neurosci. 2003 Jun;17(11):2267-76
12814360
Front Biosci. 2008 May 01;13:3423-38
18508444
Neurosci Res. 2005 Nov;53(3):221-8
16139911
J Immunol. 2006 Apr 1;176(7):3877-83
16547218
J Immunol. 2000 May 1;164(9):4893-8
10779799
Br J Pharmacol. 1998 Apr;123(7):1304-10
9579723
Physiol Rev. 2007 Apr;87(2):659-797
17429044
Prog Neurobiol. 1995 Oct;47(2):135-55
8711131
J Neuropathol Exp Neurol. 2006 Mar;65(3):199-203
16651881
Curr Opin Neurobiol. 2005 Feb;15(1):101-7
15721751
J Exp Med. 1997 Feb 3;185(3):579-82
9053458
Pharmacol Res. 1998 Nov;38(5):323-31
9806810
J Neurochem. 2007 Sep;102(5):1447-1458
17697046
J Immunol. 2007 Aug 1;179(3):1913-25
17641058
Brain Res Brain Res Rev. 2005 Apr;48(2):144-56
15850653
J Neuroimmunol. 2004 Jul;152(1-2):67-72
15223238
Curr Opin Neurobiol. 1997 Jun;7(3):346-57
9232809
Mol Cell Biol. 1996 Aug;16(8):4566-72
8754857
Cell Tissue Res. 2005 Jul;321(1):35-44
15902498
J Neurosci. 2008 Oct 29;28(44):11263-8
18971468
J Inflamm (Lond). 2007 Mar 16;4:5
17367517
Nature. 2007 Apr 26;446(7139):1091-5
17410128
Am J Obstet Gynecol. 2002 Jul;187(1):103-6
12114896
J Neurosci. 2004 Jul 14;24(28):6307-14
15254086
J Neurosci. 2008 Sep 10;28(37):9133-44
18784294
J Neural Transm (Vienna). 2008 Aug;115(8):1165-72
18506388
J Neurosci. 2008 Nov 26;28(48):12775-87
19036970
Histochem Cell Biol. 2006 Oct;126(4):453-63
16612582
J Neuropathol Exp Neurol. 2006 Nov;65(11):1090-7
17086106
J Neurochem. 2006 Jan;96(2):314-23
16336636
J Comp Neurol. 1999 Apr 28;407(1):11-32
10213185
Cell Tissue Res. 2000 Jan;299(1):105-13
10654074
J Neurochem. 2001 Sep;78(6):1339-49
11579142
Front Neuroendocrinol. 2008 Oct;29(4):507-19
18522863
Pharmacol Ther. 2006 Jan;109(1-2):210-26
16169595
Neuroscience. 2008 Oct 15;156(3):673-92
18773945
J Neurosci. 2008 May 7;28(19):4949-56
18463248
J Neurosci. 2009 Mar 25;29(12):3781-91
19321774
Glia. 2005 Nov 1;52(2):119-26
15920729
Nat Neurosci. 2006 Dec;9(12):1512-9
17115040