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Journal of Neuroinflammation

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Open Access 01-12-2023 | Epilepsy | Research

GSDMD knockdown attenuates phagocytic activity of microglia and exacerbates seizure susceptibility in TLE mice

Authors: Xiaoxia Yang, Qingqing Cao, Yi Guo, Jingchuan He, Demei Xu, Aolei Lin

Published in: Journal of Neuroinflammation | Issue 1/2023

Abstract

Background

Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Phagocytic activity of microglia is essential for clearing apoptotic neuronal debris, allowing for repair and regeneration. Our previous research has shown that gasdermin D (GSDMD)-mediated pyroptosis is involved in the pathogenesis of TLE. However, whether GSDMD-mediated pyroptosis influences the accumulation of apoptotic neurons remains unclear. Therefore, the present study was designed to investigate whether phagocytic activity of microglia is involved in GSDMD-mediated pyroptosis and the pathogenesis of TLE.

Methods

To establish a TLE model, an intra-amygdala injection of kainic acid (KA) was performed. The Racine score and local field potential (LFP) recordings were used to assess seizure severity. Neuronal death in the bilateral hippocampus was assessed by Nissl staining and TUNEL staining. Microglial morphology and phagocytic activity were detected by immunofluorescence and verified by lipopolysaccharide (LPS) and the P2Y₁₂R agonist 2MeSADP.

Results

GSDMD knockdown augmented the accumulation of apoptotic neurons and seizure susceptibility in TLE mice. Microglia activated and transition to the M1 type with increased pro-inflammatory cytokines. Furthermore, GSDMD knockdown attenuated the migration and phagocytic activity of microglia. Of note, LPS-activated microglia attenuated seizure susceptibility and the accumulation of apoptotic neurons in TLE after GSDMD knockdown. A P2Y₁₂R selective agonist, 2MeSADP, enhanced the migration and phagocytic activity of microglia.

Conclusions

Our results demonstrate that GSDMD knockdown exacerbates seizure susceptibility and the accumulation of apoptotic neurons by attenuating phagocytic activity of microglia. These findings suggest that GSDMD plays a protective role against KA-induced seizure susceptibility.

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Title: GSDMD knockdown attenuates phagocytic activity of microglia and exacerbates seizure susceptibility in TLE mice
Authors: Xiaoxia Yang
Qingqing Cao
Yi Guo
Jingchuan He
Demei Xu
Aolei Lin
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Epilepsy
Published in: Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-023-02876-w

2024 ASCO Annual Meeting

Springer Medicine

GSDMD knockdown attenuates phagocytic activity of microglia and exacerbates seizure susceptibility in TLE mice

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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