Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice.
Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice.
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DOI：
10.1002/jnr.23242
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发表时间：
2013-09
影响因子：
4.2
通讯作者：
Watters, Jyoti J.
中科院分区：
文献类型：
--
作者：
Crain, Jessica M.;Nikodemova, Maria;Watters, Jyoti J.
虽然小胶质细胞活化与所有的中枢神经系统疾病，其中许多是性二型或年龄依赖性，小胶质细胞的基础基因表达是否改变了健康的中枢神经系统中的年龄或如果它是性别依赖性的知之甚少。对3天（P3）至12个月大的雄性和雌性C57 Bl/6小鼠大脑中的小胶质细胞的分析揭示了出生后发育期间与成年期显著不同的不同基因表达谱。P3小胶质细胞的特征是iNOS、TNFα和TNF α-1 mRNA水平相对较高，而P21小胶质细胞的CD 11b、TLR 4和FcRγI表达增加。成年小胶质细胞（2-4个月）的特征在于低促炎细胞因子表达，其在12个月龄时增加。小胶质细胞基因表达的依赖性差异表明，小胶质细胞在个体发育过程中可能发生表型变化，尽管在健康大脑中，它们在任何时候都不完全表达M1或M2表型标记。有趣的是，小胶质细胞的性二态性仅在P3时，女性比男性有更高的炎症细胞因子的表达，虽然有雌激素受体的表达在这个或任何其他时间在这里评估没有性别差异。与体内小胶质细胞相比，从P3小鼠制备的原代小胶质细胞具有显著改变的基因表达，具有更高水平的TNFα、CD 11b、VEGF-1和VEGF，这表明培养可能显著改变小胶质细胞的性质。总之，基础基因表达的年龄和性别特异性差异可能使不同年龄的小胶质细胞对相同刺激的反应不同，这可能有助于改变CNS的脆弱性和/或疾病过程。
Although microglial activation is associated with all CNS disorders, many of which are sexually dimorphic or age-dependent, little is known about whether microglial basal gene expression is altered with age in the healthy CNS or if it is sex-dependent. Analysis of microglia from the brains of 3 day (P3) - to 12 month-old male and female C57Bl/6 mice revealed distinct gene expression profiles during postnatal development that differ significantly from adulthood. Microglia at P3 are characterized by relatively high iNOS, TNFα and arginase-1 mRNA levels, whereas P21 microglia have increased expression of CD11b, TLR4 and FcRγI. Adult microglia (2-4 months) are characterized by low pro-inflammatory cytokine expression that increases by 12 months of age. Age-dependent differences in microglial gene expression suggest that microglia likely undergo phenotypic changes during ontogenesis, although in the healthy brain they did not exclusively express either M1 or M2 phenotypic markers at any time. Interestingly, microglia were sexually dimorphic only at P3 when females had higher expression of inflammatory cytokines than males, although there were no sex differences in estrogen receptor expression at this or any other time evaluated here. Compared to microglia in vivo, primary microglia prepared from P3 mice had considerably altered gene expression with higher levels of TNFα, CD11b, arginase-1 and VEGF suggesting that culturing may significantly alter microglial properties. In conclusion, age- and sex-specific variances in basal gene expression may enable differential microglial responses to the same stimulus at different ages, perhaps contributing to altered CNS vulnerabilities and/or disease courses.
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影响因子：
9.3
作者：
Nikodemova M;Watters JJ
通讯作者：
Watters JJ
DOI：
10.1136/jnnp.2009.183525
发表时间：
2010-04
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Logroscino G;Traynor BJ;Hardiman O;Chiò A;Mitchell D;Swingler RJ;Millul A;Benn E;Beghi E;EURALS
通讯作者：
EURALS
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
DOI：
10.1152/ajpheart.1998.274.1.h342
发表时间：
1998-01-01
影响因子：
4.8
作者：
Chang, CI;Liao, JC;Kuo, L
通讯作者：
Kuo, L
影响因子：
4.8
作者：
Nikodemova, Maria;Watters, Jyoti J.;Duncan, Ian D.
通讯作者：
Duncan, Ian D.