A unique subtype of ramified microglia associated with synapses in the rat hippocampus

A unique subtype of ramified microglia associated with synapses in the rat hippocampus
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与大鼠海马突触相关的分支小胶质细胞的独特亚型

DOI:
10.1111/ejn.15330
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发表时间:
2021
影响因子:
3.4
通讯作者:
Jinno Shozo
Jinno Shozo
中科院分区:
医学3区
文献类型:
--
作者:
Ohgomori Tomohiro;Iinuma Kyoko;Yamada Jun;Jinno Shozo

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迄今为止,许多研究已经报道了激活的小胶质细胞的异质性。然而,越来越多的证据表明,分支的,所谓的休息,小胶质细胞也可能是异质性的,它们可能在正常的大脑稳态中发挥不同的作用。在这里,我们发现5D4硫酸角质素表位阳性(5D4+)和5D4阴性(5D4+)小胶质细胞共存于正常大鼠的海马中,而正常小鼠海马中的所有小胶质细胞均为5D4表位阴性。因此,我们的目的是确定在正常大鼠海马中与5D4表位相关的小胶质细胞的潜在异质性。光学显微镜分析显示,5D4+小胶质细胞密度在CA 3区的方向层高于其他层和区域。尽管5D4+和5D4小脑小胶质细胞都表现出分枝形态,但三维重建分析显示,5D4+中的节点数、末端数和突起的复杂性高于5D4小脑小胶质细胞。线性判别分析表明,5D4+和5D4 β小胶质细胞可以分为不同的形态学亚型。5D4+小胶质细胞中突触终末和小胶质细胞突起之间的接触比例高于5D4+小胶质细胞。促炎细胞因子白细胞介素-1 β和嘌呤能受体P2 Y12(P2 Y12 R)的基因表达在5D4+中高于5D4+小胶质细胞。总之,这些结果表明,至少有两种不同亚型的分支小胶质细胞共存于正常大鼠海马,也表明,5D4+小胶质细胞可能代表一个独特的亚型与突触。
To date, a number of studies have reported the heterogeneity of activated microglia. However, there is increasing evidence suggests that ramified, so‐called resting, microglia may also be heterogeneous, and they may play diverse roles in normal brain homeostasis. Here, we found that both 5D4 keratan sulfate epitope‐positive (5D4+) and 5D4‐negative (5D4‒) microglia coexisted in the hippocampus of normal rats, while all microglia were negative for the 5D4 epitope in the hippocampus of normal mice. We thus aimed to determine the potential heterogeneity of microglia related to the 5D4 epitope in the normal rat hippocampus. The optical disector analysis showed that the densities of 5D4+microglia were higher in the stratum oriens of the CA3 region than in other layers and regions. Although both 5D4+and 5D4‒microglia exhibited a ramified morphology, the three‐dimensional reconstruction analysis showed that the node numbers, end numbers, and complexity of processes were higher in 5D4+than in 5D4‒microglia. The linear discriminant analysis showed that 5D4+and 5D4‒microglia can be classified into distinct morphometric subtypes. The ratios of contact between synaptic boutons and microglial processes were higher in 5D4+than in 5D4‒microglia. The gene expressions of pro‐inflammatory cytokine interleukin‐1β and purinergic receptor P2Y12(P2Y12R) were higher in 5D4+than in 5D4‒microglia. Together, these results indicate that at least two different subtypes of ramified microglia coexist in the normal rat hippocampus and also suggest that 5D4+microglia may represent a unique subtype associated with synapses.
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