Status epilepticus induced Gadd45b is required for augmented dentate neurogenesis

被引:5
|
作者
Xiao, Xin-Li [1 ,2 ,3 ]
Wu, Xiao-Lin [2 ,3 ]
Yang, Peng-Bo [3 ]
Hu, Hai-Bo [3 ]
Chen, Yu [1 ,2 ]
Min-Li [1 ,2 ]
Si, Kai-Wei [4 ]
Wu, Feng [5 ]
Liu, Jian-Xin [1 ,2 ]
机构
[1] Xi An Jiao Tong Univ, Sch Basic Med Sci, Inst Neurobiol, Hlth Sci Ctr, 76 West Yanta Rd, Xian 710061, Peoples R China
[2] Xi An Jiao Tong Univ, Inst Neurosci, Translat Med Inst, Hlth Sci Ctr, 76 West Yanta Rd, Xian 710061, Peoples R China
[3] Xi An Jiao Tong Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Human Anat Histol & Embryol, 76 West Yanta Rd, Xian 710061, Peoples R China
[4] Xi An Jiao Tong Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Pathogen Biol & Immunol, 76 West Yanta Rd, Xian 710061, Peoples R China
[5] Xi An Jiao Tong Univ, Ctr Teaching & Expt Med Post Grad, Hlth Sci Ctr, 76 West Yanta Rd, Xian 710061, Peoples R China
基金
中国国家自然科学基金;
关键词
Status Epilepticus; Dentate Neurogenesis; DNA Demethylation; Neurotrophic factors; DNA METHYLATION; SEIZURES; REORGANIZATION; HIPPOCAMPUS; ACTIVATION; EXPRESSION; PROTEINS; PLAYERS; CELLS; MODEL;
D O I
10.1016/j.scr.2020.102102
中图分类号
Q813 [细胞工程];
学科分类号
摘要
In animal models with temporal lobe epilepsy (TLE), the status epilepticus (SE) leads to a dramatic increase in number of newly born neuron in the subgranular zone (SGZ) of dentate gyms. How the SE confers a modulation in the dentate neuro-genesis is mostly unknown. Gadd45b is involved in epigenetic gene activation by DNA demethylation. This study was performed to present a novel mechanism underling SE-induced dentate neurogenesis. A transient induction (12 hrs to 3 days) of Gadd45b was observed in dentate gyms of mice after pilocarpine-induced SE. Labeling the dividing cells with BrdU, we next found that the induction of Gadd45b was required to increase the rate of cell proliferation in the dentate gyrus at 7 and 14 days after SE. Afterward, the DNA methylation levels for candidate growth factor genes critical for the adult neurogenesis were assayed with Sequenom MassARRAY Analyzer. The results indicated that Gadd45b was necessary for SE-induced DNA demethylation of specific promoters and expression of corresponding genes in the dentate gyrus, including brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2). Using Timm staining, we further suggested that SE-induced Gadd45b might contribute to the subsequent mossy fiber sprouting (MFS) in the chronically epileptic hippocampus via epigenetic regulation of dentate neurogenesis at early stage after SE. Together, Gadd45b links pilocarpine-induced SE to epigenetic DNA modification of secreted factors in the dentate gyrus, leading to extrinsic modulation on the neurogenesis.
引用
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页数:12
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