A MATLAB-based program for three-dimensional quantitative analysis of micronuclei reveals that neuroinflammation induces micronuclei formation in the brain.

A MATLAB-based program for three-dimensional quantitative analysis of micronuclei reveals that neuroinflammation induces micronuclei formation in the brain.
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DOI:
10.1038/s41598-021-97640-6
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发表时间:
2021-09-15
期刊:
影响因子:
4.6
通讯作者:
Tsuruta F
Tsuruta F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yano S;Akiyama K;Tsuchiya R;Kubotani H;Chiba T;Nagata T;Tsuruta F

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已知微核是基因组不稳定性的生物标志物,基因组不稳定性是肿瘤和衰老的标志。正常情况下,微核是由分离错误和分裂或迁移细胞产生的机械应力产生的,导致先天免疫反应途径激活。虽然微核经常出现在受损组织中,但准确分析微核的定量方法一直存在问题。在这里,我们介绍了一种新的基于MATLAB的程序,用于定量微核(CAMDi:计算自动微核区分)在体外和体内。CAMDi适用于各种实验成像技术,并可用于获得可重复的数据。CAMDi使我们能够从三维图像中测量微核的准确大小。使用CAMDi,我们揭示了微核的出现和神经炎症之间的新联系。我们发现,炎症刺激不会增加原代神经元的微核数。另一方面,给予小鼠脂多糖会轻微增加海马区神经元的微核形成。这些结果表明,神经元微核形成是由炎症反应以非细胞自主方式诱导的。我们提供了一种新的工具,CAMDi,以量化微核,并证明,神经元微核的产生不仅是由细胞自主的过程,但也通过与体内神经炎症相关的细胞间通讯。
The micronucleus is known to be a biomarker for genomic instability, which is a hallmark of tumors and aging. Normally, micronuclei are produced by segregation errors and mechanical stresses arising from dividing or migrating cells, leading to activation of the innate immune response pathway. Although micronuclei often emerge in damaged tissues, the quantitative procedure for analyzing micronuclei accurately has been problematic. Here, we introduce a novel MATLAB-based program for quantifying micronuclei (CAMDi: calculating automatic micronuclei distinction) in vitro and in vivo. CAMDi is adaptable to various experimental imaging techniques and is useful for obtaining reproducible data. CAMDi enables us to measure the accurate size of micronuclei from the three-dimensional images. Using CAMDi, we revealed a novel link between the emergence of micronuclei and neuroinflammation. We found that inflammatory stimulation does not increase the number of micronuclei in primary neurons. On the other hand, the administration of lipopolysaccharide into mice slightly increases micronuclei formation in neurons of the hippocampus region. These findings demonstrate that neuronal micronuclei formations are induced by an inflammatory response in a non-cell-autonomous manner. We provide a novel tool, CAMDi, to quantify micronuclei and demonstrate that neuronal micronuclei are produced not only by the cell-autonomous process but also by the intercellular communication associated with neuroinflammation in vivo.
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