Age Influences Microglial Activation After Cuprizone-Induced Demyelination.
Age Influences Microglial Activation After Cuprizone-Induced Demyelination.
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DOI：
10.3389/fnagi.2018.00278
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发表时间：
2018
影响因子：
4.8
通讯作者：
Aigner L
中科院分区：
文献类型：
--
作者：
Klein B;Mrowetz H;Barker CM;Lange S;Rivera FJ;Aigner L
多发性硬化（MS）是一种慢性炎症性CNS疾病，其引起脱髓鞘病变并损害白色和灰质区域。衰老是MS进展的重要因素，而小胶质细胞（CNS组织的免疫细胞）在所有疾病阶段都起着重要作用。在衰老过程中，小胶质细胞的功能发生了变化。这些年龄相关的变化可能已经在早期开始，并可能影响CNS病理的进展。本研究的目的是调查中年中枢神经系统中的小胶质细胞是否对脱髓鞘反应不同。为此，几种小胶质细胞标记物（离子钙结合衔接分子1（Iba-1），P2 RY 12，F4/80，CD 68，主要组织相容性复合物II（MHCII），具有胶原结构的巨噬细胞受体（Marco），转运蛋白18 kD（TSPO），CD 206，和CD 163）在年轻（2月龄）和中年（10月龄）小鼠的急性二腙脱髓鞘模型中进行分析。此外，使用增殖细胞核抗原（PCNA）和溴脱氧尿苷（BrdU），这是注射的髓鞘再生的发病双标记的小胶质细胞增殖进行定量。为了比较年龄相关的小胶质细胞的变化，在脱髓鞘和髓鞘再生的灰色和白色的问题，门的背海马齿状回（DG）和压部的胼胝体（CC）进行了平行分析。健康对照组的小胶质细胞中的神经胶质细胞相关变化在分析的灰质区域中更明显（中年小鼠中F4/80和Marco水平较高以及CD 68表达较低）。在脱髓鞘和髓鞘再生过程中，在年轻组的压部观察到小胶质细胞标记物Iba-1、CD 68和TSPO的更强的增加。脱髓鞘过程中P2 RY 12显著减少，但这是年龄和区域依赖性的。在中年组中，抗炎标志物CD 206和CD 163的诱导作用更强，但在两个分析区域之间也存在差异。脱髓鞘和髓鞘再生导致PCNA+小胶质细胞显着增加，只有在年轻组内的白色物质区域。BrdU+小胶质细胞的数量在脱髓鞘或髓鞘再生过程中没有变化。这些结果清楚地表明，小胶质细胞在中年期间已经改变，并且对CNS脱髓鞘的反应也不同，然而，这是高度区域依赖性的。
Multiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes demyelinated lesions and damages white and gray matter regions. Aging is a significant factor in the progression of MS, and microglia, the immune cells of the CNS tissue, play an important role in all disease stages. During aging, microglia are functionally altered. These age-related changes probably already begin early and might influence the progression of CNS pathologies. The aim of the present study was to investigate whether microglia in the middle-aged CNS already react differently to demyelination. For this purpose, several microglia markers (ionized calcium binding adaptor molecule 1 (Iba-1), P2RY12, F4/80, CD68, major histocompatibility complex II (MHCII), macrophage receptor with collagenous structure (Marco), Translocator protein 18 kD (TSPO), CD206, and CD163) were analyzed in the acute cuprizone demyelination model in young (2-month-old) and middle-aged (10-month-old) mice. In addition, microglial proliferation was quantified using double-labeling with proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), which was injected with the onset of remyelination. To compare age-related microglial changes during de- and remyelination in both gray and white matter, the hilus of the dorsal hippocampal dentate gyrus (DG) and the splenium of the corpus callosum (CC) were analyzed in parallel. Age-related changes in microglia of healthy controls were more pronounced in the analyzed gray matter region (higher levels of F4/80 and Marco as well as lower expression of CD68 in middle-aged mice). During de- and remyelination, a stronger increase of the microglial markers Iba-1, CD68 and TSPO was observed in the splenium of the younger groups. There was a significant reduction of P2RY12 during demyelination, however, this was age- and region-dependent. The induction of the anti-inflammatory markers CD206 and CD163 was stronger in the middle-aged group, but also differed between the two analyzed regions. De- and remyelination led to a significant increase in PCNA+ microglia only in young groups within the white matter region. The number of BrdU+ microglia was not changed during de- or remyelination. These results clearly show that microglia are already altered during middle-age and also react differently to CNS demyelination, however, this is highly region-dependent.
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影响因子：
5.4
作者：
Gordon, Siamon;Hamann, Joerg;Stacey, Martin
通讯作者：
Stacey, Martin
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
影响因子：
3.1
作者：
Goldberg, Johannes;Clarner, Tim;Kipp, Markus
通讯作者：
Kipp, Markus
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y