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<p>The mechanisms underlying seizure-induced cortical injury in status epilepticus-related experimental epilepsy remain incompletely understood, and upstream regulators of inflammasome activation require further clarification. By combining bioinformatics screening with in vivo validation, we examined whether the MTRNR2L1/MTRNR2L10 axis is associated with NLRP3 inflammasome-related signaling in the cerebral cortex of rats subjected to status epilepticus, with the goal of identifying candidate regulators of seizure-induced cortical injury. The GSE134697 dataset was obtained from GEO. Differentially expressed genes (DEGs) were screened using |log2FC|&gt;4 and adjusted <i>P</i> &lt; 0.05. GO/KEGG enrichment analyses, together with a STRING-based protein–protein interaction (PPI) network, prioritized MTRNR2L1/MTRNR2L10 as candidate molecules annotated to the “regulation of signal transduction” pathway for subsequent in vivo validation. Ninety SPF SD rats (10 per group) were used: a basic model module (normal, sham, and EP model) and a target-intervention module (six groups: negative control, overexpression, and knockdown for MTRNR2L1/MTRNR2L10). Behavioral scoring, histopathology, Western blotting, co-immunoprecipitation, and ELISA were performed. Fifty-one DEGs were identified. Among them, only MTRNR2L1/MTRNR2L10 mapped to signal-transduction regulation associated with EP, and their cortical expression in EP rats fell to &lt; 30% of control. Upregulating this axis lowered Racine seizure scores and neurological deficit scores, was associated with reduced NLRP3 inflammasome-related marker expression, mitigated the loss of BBB-related tight-junction protein markers, and reduced cortical neuronal apoptosis. In contrast, silencing either target exacerbated these changes, and co-immunoprecipitation suggested that the two molecules were associated within the same protein complex. The MTRNR2L1/MTRNR2L10 axis may act as a candidate protective regulator in status epilepticus-related experimental epilepsy, in association with reduced NLRP3 inflammasome-related signaling. These findings support further mechanistic evaluation of MTRNR2L1/MTRNR2L10 in seizure-induced cortical injury, but do not establish these molecules as therapeutic targets for drug-resistant epilepsy.</p>

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Integrated Bioinformatics and in vivo Validation Identify the MTRNR2L1/MTRNR2L10 Axis as a Candidate Regulator Associated with Cortical NLRP3 Inflammasome-Related Signaling in Experimental Epilepsy

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Hong Gao,
  • Ranze Cai,
  • Qiuping Li,
  • Shuangchen Liu,
  • Xiaojun Zhu

摘要

The mechanisms underlying seizure-induced cortical injury in status epilepticus-related experimental epilepsy remain incompletely understood, and upstream regulators of inflammasome activation require further clarification. By combining bioinformatics screening with in vivo validation, we examined whether the MTRNR2L1/MTRNR2L10 axis is associated with NLRP3 inflammasome-related signaling in the cerebral cortex of rats subjected to status epilepticus, with the goal of identifying candidate regulators of seizure-induced cortical injury. The GSE134697 dataset was obtained from GEO. Differentially expressed genes (DEGs) were screened using |log2FC|>4 and adjusted P < 0.05. GO/KEGG enrichment analyses, together with a STRING-based protein–protein interaction (PPI) network, prioritized MTRNR2L1/MTRNR2L10 as candidate molecules annotated to the “regulation of signal transduction” pathway for subsequent in vivo validation. Ninety SPF SD rats (10 per group) were used: a basic model module (normal, sham, and EP model) and a target-intervention module (six groups: negative control, overexpression, and knockdown for MTRNR2L1/MTRNR2L10). Behavioral scoring, histopathology, Western blotting, co-immunoprecipitation, and ELISA were performed. Fifty-one DEGs were identified. Among them, only MTRNR2L1/MTRNR2L10 mapped to signal-transduction regulation associated with EP, and their cortical expression in EP rats fell to < 30% of control. Upregulating this axis lowered Racine seizure scores and neurological deficit scores, was associated with reduced NLRP3 inflammasome-related marker expression, mitigated the loss of BBB-related tight-junction protein markers, and reduced cortical neuronal apoptosis. In contrast, silencing either target exacerbated these changes, and co-immunoprecipitation suggested that the two molecules were associated within the same protein complex. The MTRNR2L1/MTRNR2L10 axis may act as a candidate protective regulator in status epilepticus-related experimental epilepsy, in association with reduced NLRP3 inflammasome-related signaling. These findings support further mechanistic evaluation of MTRNR2L1/MTRNR2L10 in seizure-induced cortical injury, but do not establish these molecules as therapeutic targets for drug-resistant epilepsy.