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癫痫GASH/Sal模型下丘听觉源性点燃后蛋白质组学图谱的变化

Changes in the Proteomic Profile After Audiogenic Kindling in the Inferior Colliculus of the GASH/Sal Model of Epilepsy.

作者信息

Zeballos Laura, García-Peral Carlos, Ledesma Martín M, Auzmendi Jerónimo, Lazarowski Alberto, López Dolores E

机构信息

Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, 37007 Salamanca, Spain.

Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.

出版信息

Int J Mol Sci. 2025 Mar 5;26(5):2331. doi: 10.3390/ijms26052331.

DOI:10.3390/ijms26052331
PMID:40076950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11900993/
Abstract

Epilepsy is a multifaceted neurological disorder characterized by recurrent seizures and associated with molecular and immune alterations in key brain regions. The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca), a genetic model for audiogenic epilepsy, provides a powerful tool to study seizure mechanisms and resistance in predisposed individuals. This study investigates the proteomic and immune responses triggered by audiogenic kindling in the inferior colliculus, comparing non-responder animals exhibiting reduced seizure severity following repeated stimulation versus GASH/Sal naïve hamsters. To assess auditory pathway functionality, Auditory Brainstem Responses (ABRs) were recorded, revealing reduced neuronal activity in the auditory nerve of non-responders, while central auditory processing remained unaffected. Cytokine profiling demonstrated increased levels of proinflammatory markers, including IL-1 alpha (Interleukin-1 alpha), IL-10 (Interleukin-10), and TGF-beta (Transforming Growth Factor beta), alongside decreased IGF-1 (Insulin-like Growth Factor 1) levels, highlighting systemic inflammation and its interplay with neuroprotection. Building on these findings, a proteomic analysis identified 159 differentially expressed proteins (DEPs). Additionally, bioinformatic approaches, including Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), revealed disrupted pathways related to metabolic and inflammatory epileptic processes and a module potentially linked to a rise in the threshold of seizures, respectively. Differentially expressed genes, identified through bioinformatic and statistical analyses, were validated by RT-qPCR. This confirmed the upregulation of six genes (-Glypican-1; -Syndecan-3; -Nerve Growth Factor Inducible; -Copine 5; -Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and -Dipeptidyl Peptidase 8) and the downregulation of two (-RAS-like proto-oncogene B-and -S100 calcium-binding protein B), aligning with reduced seizure severity. This study may uncover key proteomic and immune mechanisms underlying seizure susceptibility, providing possible novel therapeutic targets for refractory epilepsy.

摘要

癫痫是一种多方面的神经系统疾病，其特征为反复发作的癫痫，且与关键脑区的分子和免疫改变相关。遗传性听源性癫痫仓鼠（GASH/Sal，Genetic Audiogenic Seizure Hamster, Salamanca）作为听源性癫痫的一种遗传模型，为研究易患个体的癫痫发作机制和耐受性提供了一个强大工具。本研究调查了下丘中听源性点燃引发的蛋白质组学和免疫反应，比较了在反复刺激后癫痫发作严重程度降低的无反应动物与未接触过的GASH/Sal仓鼠。为评估听觉通路功能，记录了听觉脑干反应（ABR），结果显示无反应动物的听神经中神经元活动减少，而中枢听觉处理未受影响。细胞因子分析表明促炎标志物水平升高，包括白细胞介素-1α（IL-1 alpha）、白细胞介素-10（IL-10）和转化生长因子-β（TGF-beta），同时胰岛素样生长因子-1（IGF-1）水平降低，突出了全身炎症及其与神经保护的相互作用。基于这些发现，蛋白质组学分析鉴定出159种差异表达蛋白（DEP）。此外，生物信息学方法，包括基因集富集分析（GSEA）和加权基因共表达网络分析（WGCNA），分别揭示了与代谢性和炎症性癫痫过程相关的通路破坏以及一个可能与癫痫发作阈值升高相关的模块。通过生物信息学和统计分析鉴定出的差异表达基因，经逆转录定量聚合酶链反应（RT-qPCR）验证。这证实了六个基因（磷脂酰肌醇蛋白聚糖-1；多配体蛋白聚糖-3；神经生长因子诱导蛋白；钙磷脂结合蛋白5；含GTP酶结构域、ANK重复序列和PH结构域的Arf-GAP蛋白2；以及二肽基肽酶8）的上调和两个基因（RAS样原癌基因B和S100钙结合蛋白B）的下调，这与癫痫发作严重程度降低一致。本研究可能揭示癫痫易感性背后的关键蛋白质组学和免疫机制，为难治性癫痫提供可能的新治疗靶点。

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本文引用的文献

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Commun Biol. 2024 Oct 31;7(1):1422. doi: 10.1038/s42003-024-07110-8.
2
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3
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Int J Mol Sci. 2024 Jun 12;25(12):6488. doi: 10.3390/ijms25126488.
4
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Epilepsy Behav. 2024 Aug;157:109890. doi: 10.1016/j.yebeh.2024.109890. Epub 2024 Jun 20.
5
Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1 and Prolactin.神经退行性痴呆症中的血浆生物标志物：揭示血清催产素、BDNF、NPTX1、TREM2、TNF-α、IL-1 和催乳素的潜在作用。
Curr Alzheimer Res. 2024;21(2):109-119. doi: 10.2174/0115672050313419240520051751.
6
Audiogenic kindling activates glutamatergic system in the hippocampus of rats with genetic predisposition to audiogenic seizures.听源性点燃激活了对听源性癫痫发作具有遗传易感性的大鼠海马中的谷氨酸能系统。
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7
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8
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Nat Neurosci. 2023 Dec;26(12):2237-2249. doi: 10.1038/s41593-023-01469-3. Epub 2023 Oct 26.
9
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10
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