Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation
10.3760/cma.j.cn112151-20231110-00348
- VernacularTitle:低压低氧刺激后小鼠小脑中RNA m6A甲基化调控因子表达的变化
- Author:
Lingfeng XIAO
1
;
Chunhui MA
;
Shunli ZHAO
;
Qing LI
;
Chunying LIU
;
Yamei NIU
;
Weimin TONG
Author Information
1. 中国医学科学院基础医学研究所暨北京协和医学院基础学院病理学系，北京 100005
- Keywords:
Cerebellum;
Cell hypoxia;
RNA methylation;
Methyltransferases
- From:
Chinese Journal of Pathology
2024;53(5):452-457
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.
