Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions.
Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions.
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DOI：
10.1186/s12974-021-02252-6
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发表时间：
2021-09-22
影响因子：
9.3
通讯作者：
Kelly MP
中科院分区：
文献类型：
--
作者：
Porcher L;Bruckmeier S;Burbano SD;Finnell JE;Gorny N;Klett J;Wood SK;Kelly MP
尽管人们普遍认为神经炎症会导致与年龄相关的认知能力下降，但比较年轻人与老年人大脑中细胞因子蛋白表达的研究在细胞因子和研究的大脑区域数量方面令人惊讶地有限。更复杂的是，大量的差异-特别是白细胞介素6（IL-6）-可能是由于性别，物种/品系和/或大脑区域的差异。因此，我们通过使用Bioplex和Western印迹法，使用2种内部饲养的小鼠品系以及从NIA获得的大鼠，测量两种性别的几个脑区域中的多种细胞因子，阐明了细胞因子表达如何随年龄变化。酌情使用参数和非参数统计检验。在C57 BL/6 J小鼠的腹侧海马中，我们发现IL-1α、IL-1β、IL-2、IL-3、IL-4、IL-6、IL-9、IL-10、IL-12 p40、IL-12 p70、IL-13、IL-17、嗜酸性粒细胞趋化因子、G-CSF、白细胞介素δ、KC、MIP-1a、MIP-1b、rantes和TNFα的年龄相关性增加通常在雌性小鼠中更明显，但IL-5、MCP-1或GM-CSF无年龄相关变化。我们还发现，衰老与一个模块的出现有着独特的联系。网络），以及腹侧海马中IL-10和IL-1β从糖基化到非糖基化亚型的年龄相关转变。有趣的是，海马外细胞因子表达的年龄相关性增加更为谨慎，雄性和雌性C57 BL/6 J小鼠的前额叶皮质、纹状体和小脑表现出IL-6表达的强烈年龄相关性增加，但IL-1β表达没有。重要的是，我们发现这种广泛的与年龄相关的IL-6增加也发生在BALB/cJ小鼠和Brown Norway大鼠中，表明了物种和饲养环境的保护。因此，与其他脑区相比，海马中细胞因子的年龄相关性增加更明显，并且根据脑区、遗传背景和检查的细胞因子，女性与男性相比可能更明显。在线版本包含补充材料，可通过10.1186/s12974-021-02252-6获得。
Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound—particularly for interleukin 6 (IL-6)—possibly due to differences in sex, species/strain, and/or the brain regions studied. As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate. In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1β in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1β. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments. Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined. The online version contains supplementary material available at 10.1186/s12974-021-02252-6.
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DOI：
10.1084/jem.20131219
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bouchlaka MN;Sckisel GD;Chen M;Mirsoian A;Zamora AE;Maverakis E;Wilkins DE;Alderson KL;Hsiao HH;Weiss JM;Monjazeb AM;Hesdorffer C;Ferrucci L;Longo DL;Blazar BR;Wiltrout RH;Redelman D;Taub DD;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
3.7
作者：
Chen J;Zhou X;Zeng M;Wu X
通讯作者：
Wu X
DOI：
10.1523/jneurosci.2173-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barrientos RM;Hein AM;Frank MG;Watkins LR;Maier SF
通讯作者：
Maier SF
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
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.