GSDMD knockdown exacerbates hippocampal damage and seizure susceptibility by crosstalk between pyroptosis and apoptosis in kainic acid-induced temporal lobe epilepsy

红藻氨酸 癫痫 海马结构 上睑下垂 基因敲除 癫痫发生 神经科学 细胞凋亡 发病机制 细胞生物学 生物 程序性细胞死亡 免疫学 生物化学 谷氨酸受体 受体
作者
Aolei Lin,Yi Guo,Hui Zhang,Peijia Lin,Kaiyan Tao,Li Jiang,Dan Xu,Bin Chen
出处
期刊:Biochimica Et Biophysica Acta: Molecular Basis Of Disease [Elsevier]
卷期号:1869 (5): 166687-166687 被引量:2
标识
DOI:10.1016/j.bbadis.2023.166687
摘要

Neuronal loss is a vital pathological feature of temporal lobe epilepsy (TLE). However, the exact mechanism of neuronal loss in TLE is not fully understood. Pyroptosis, a novel form of programmed cell death (PCD), has been considered a contributor to the pathogenesis of TLE. However, recent studies have implicated extensive molecular crosstalk among pyroptosis, apoptosis, and necroptosis in various diseases, and they can be transformed to each other according to different contexts. This study aimed to investigate whether gasdermin D (GSDMD)-mediated pyroptosis is involved in the pathogenesis of TLE and whether crosstalk exists in the process of the modulation of pyroptosis.The TLE model was established by intra-amygdala injection of kainic acid. The Racine score and local field potential (LFP) recordings were used to assess seizure severity. Western blotting and immunofluorescence were applied to detect the levels and cellular localization of GSDMD. The neuronal loss and type of neuronal death in the bilateral hippocampus were assessed by Nissl staining and flow cytometry analysis. The underlying crosstalk among pyroptosis, apoptosis, and necroptosis was explored by western blot and verified by VX765.GSDMD was significantly upregulated and mainly expressed within the neurons of the hippocampus in the TLE model. Inhibition of pyroptosis by GSDMD knockdown triggered caspase-3-mediated apoptosis, leading to excess neuronal loss and deterioration of epileptic behaviors. Blocking caspase-1 markedly inhibited caspase-3-mediated apoptosis and improved epileptic behaviors under GSDMD knockdown.Our results demonstrate that GSDMD-mediated pyroptosis is involved in the pathogenesis of TLE. However, inhibition of GSDMD triggers caspase-1-mediated crosstalk between pyroptosis and apoptosis, which exacerbates neuronal loss and seizure susceptibility. Therefore, the complex crosstalk among different forms of PCD should be considered when a potential molecular target in the single PCD pathway is modulated. On the other hand, along with further studies of molecular crosstalk among the PCD pathways, taking advantage of crosstalk to attenuate neuronal loss may provide new insight for the clinical therapy of TLE.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
lycoris完成签到,获得积分10
1秒前
lemon发布了新的文献求助10
1秒前
ybb关注了科研通微信公众号
2秒前
大个应助Wdw2236采纳,获得10
3秒前
Z_发布了新的文献求助10
3秒前
4秒前
小蝶完成签到,获得积分10
4秒前
彪壮的未来完成签到,获得积分10
4秒前
6秒前
vivid发布了新的文献求助10
6秒前
Shawn完成签到 ,获得积分10
8秒前
9秒前
传奇3应助yyyyyy采纳,获得10
9秒前
Hello应助chemwang采纳,获得10
9秒前
10秒前
juziyaya应助海绵体宝宝采纳,获得30
11秒前
11秒前
12秒前
HU发布了新的文献求助10
13秒前
ybb发布了新的文献求助10
14秒前
14秒前
老张完成签到,获得积分20
15秒前
Wdw2236发布了新的文献求助10
16秒前
微笑枫完成签到,获得积分10
16秒前
香蕉秋柳发布了新的文献求助10
17秒前
17秒前
cjf完成签到,获得积分20
17秒前
18秒前
18秒前
18秒前
jie发布了新的文献求助10
18秒前
cjf发布了新的文献求助10
21秒前
ayayaya完成签到 ,获得积分10
21秒前
小蝶发布了新的文献求助10
23秒前
yyyyyy发布了新的文献求助10
23秒前
心灵美的飞机完成签到,获得积分20
25秒前
lemon完成签到 ,获得积分10
27秒前
香蕉秋柳完成签到,获得积分10
29秒前
李健应助淡定电脑采纳,获得10
29秒前
小二郎应助负责冰烟采纳,获得10
29秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3245744
求助须知:如何正确求助?哪些是违规求助? 2889446
关于积分的说明 8258420
捐赠科研通 2557794
什么是DOI,文献DOI怎么找? 1386625
科研通“疑难数据库(出版商)”最低求助积分说明 650327
邀请新用户注册赠送积分活动 626675