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脂质过氧化通过激活脑积水患者的WNT/β-连环蛋白信号通路诱导反应性星形胶质细胞增生。

Lipid Peroxidation Induces Reactive Astrogliosis by Activating WNT/β-Catenin Pathway in Hydrocephalus.

作者信息

Suryaningtyas Wihasto, Parenrengi Muhammad Arifin, Bajamal Abdul Hafid, Rantam Fedik Abdul

机构信息

Department of Neurosurgery, Faculty of Medicine Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia.

Department of Veterinary Microbiology, Faculty of Veterinary Medicine and Laboratory for Stem Cell Research, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.

出版信息

Malays J Med Sci. 2020 May;27(3):34-42. doi: 10.21315/mjms2020.27.3.4. Epub 2020 Jun 30.

DOI:10.21315/mjms2020.27.3.4
PMID:32684804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7337957/
Abstract

BACKGROUND

Hydrocephalus induces mechanical and biochemical changes in neural cells of the brain. Astrogliosis, as the hallmark of cellular changes in white matter, is involved in demyelination process, re-myelination inhibitory effect, and inhibition of axonal elongation and regeneration. The pathophysiology of this process is not well understood. The purpose of the present study is to elucidate the effect of lipid peroxidation product on astrogliosis through WNT/ β-catenin in kaolin-induced hydrocephalic rats.

METHODS

The study used kaolin-induced hydrocephalic rats. Obstructive hydrocephalus was expected to develop within seven days after induction. The hydrocephalus animals were killed at day 7, 14 and 21 after induction. One group of the saline-injected animals was used for sham-treatment.

RESULTS

We demonstrated that the hydrocephalic rats exhibited a high expression of 4-hydroxynonenal (4-HNE) in the periventricular area. The expression of β-catenin also increased, following the pattern of 4-HNE. Reactive astrocyte, expressed by positive glial fibrillary acidic protein (GFAP), was upregulated in an incremental fashion as well as the microglia.

CONCLUSION

This work suggests that lipid peroxidation product, 4-HNE, activated the WNT/β-catenin pathway, leading to the development of reactive astrocyte and microglia activation in hydrocephalus.

摘要

背景

脑积水会在脑内神经细胞中引发机械和生化变化。星形胶质细胞增生作为白质细胞变化的标志，参与脱髓鞘过程、再髓鞘化抑制作用以及轴突伸长和再生的抑制。这一过程的病理生理学尚未完全明了。本研究的目的是通过WNT/β-连环蛋白通路阐明脂质过氧化产物对高岭土诱导的脑积水大鼠星形胶质细胞增生的影响。

方法

本研究使用高岭土诱导的脑积水大鼠。预计在诱导后7天内发生梗阻性脑积水。在诱导后第7、14和21天处死脑积水动物。一组注射生理盐水的动物用于假处理。

结果

我们证明脑积水大鼠在脑室周围区域表现出4-羟基壬烯醛（4-HNE）的高表达。β-连环蛋白的表达也随着4-HNE的模式增加。由胶质纤维酸性蛋白（GFAP）阳性表达的反应性星形胶质细胞以及小胶质细胞均呈递增式上调。

结论

本研究表明脂质过氧化产物4-HNE激活了WNT/β-连环蛋白通路，导致脑积水时反应性星形胶质细胞的发展和小胶质细胞的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/6761cb197f6c/04mjms2703_oa1f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/b499895e29e9/04mjms2703_oa1f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/b257e6bc967b/04mjms2703_oa1f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/6761cb197f6c/04mjms2703_oa1f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/b499895e29e9/04mjms2703_oa1f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/b257e6bc967b/04mjms2703_oa1f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d7/7337957/6761cb197f6c/04mjms2703_oa1f3.jpg

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Neurotoxic reactive astrocytes are induced by activated microglia.神经毒性反应性星形胶质细胞由活化的小胶质细胞诱导产生。
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