耐药癫痫患者腺苷信号通路的临床遗传学分析。

IF 1.9 4区 医学 Q3 CLINICAL NEUROLOGY
Annals of Indian Academy of Neurology Pub Date : 2025-01-01 Epub Date: 2025-02-14 DOI:10.4103/aian.aian_358_24
Vikas Dhiman, Kalpita Karan, Parthasarathy Satischandra, Anita Mahadevan, Arivazhagan Arimappamagan, Rose D Bharath, Dharma Raj, Kandavel Thennarasu, Lakshminarayanpuram G Viswanathan, Ravindranadh Mundlamuri, Raghavendra Kenchaiah, Ajay Asranna, Jitender Saini, Jamuna R Rajeswaran, Keshav Kumar, Malla Bhaskara Rao, Anuranjan Anand, Sanjib Sinha
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引用次数: 0

摘要

背景与目的:腺苷途径在海马硬化(HS)致耐药癫痫(DRE)中的作用尚不明确。本研究旨在为腺苷途径在DRE合并HS (re -HS)患者中的作用提供新的见解。方法:采用定量聚合酶链反应和免疫组织化学方法分析手术切除的硬化海马(n = 37)中参与腺苷途径的10个基因(ADARB1、ADK、NT5E、ADORA1、C-FOS、C-MYC、CREB1、C-JUN、NF-kB1和MAPK)的表达,并与尸检获得的对照海马(n = 38)进行比较。在20名匹配患者和30名健康对照者的外周血中也进行了表达分析。结果:C-JUN、NT5E、C-FOS、ADARB1、ADORA1在海马中显著上调,而C-JUN、NT5E、C-FOS、ADORA1在血液中显著下调。ADARB1、NF-kB1、MAPK1、C-FOS、CREB1在术后血液样本中表达方向相反。在临床遗传学分析中,MAPK1和ADARB1与齿状回神经元分散相关(P分别为0.02和0.03),C-JUN与CA1区和CA4区神经元丢失相关(P = 0.01)。在血液中,MAPK1、NF-kB1和C-FOS的表达与癫痫发作年龄呈负相关(P分别为0.02、0.03和0.03)。此外,ADARB1表达与CA3和CA4区神经元损失相关(P分别≤0.001和0.04)。结论:在脑和外周血中具有相似表达模式的基因是DRE-HS的潜在生物标志物。显著的临床-遗传相关性为进一步研究开发新的治疗干预措施提供了依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinico-genetic Analysis of Adenosine Signaling Pathway in Drug-Resistant Epilepsy.

Background and objectives: The adenosine pathway in drug-resistant epilepsy (DRE) due to hippocampal sclerosis (HS) is largely unexplored. The present study aims to provide new insights into the role of adenosine pathway in patients with DRE associated with HS (DRE-HS).

Methods: Quantitative polymerase chain reaction and immunohistochemistry were used to analyze 10 genes involved in adenosine pathway ( ADARB1 , ADK , NT5E , ADORA1 , C-FOS, C-MYC, CREB1, C-JUN, NF-kB1, and MAPK ) in surgically resected sclerosed hippocampi (n = 37) and compare their expressions with control hippocampi (n = 38) obtained from the autopsy. Expression analyses were also carried out in peripheral blood of 20 matched patients and 30 healthy controls.

Results: C-JUN , NT5E , C-FOS , ADARB1 , and ADORA1 were significantly upregulated in the hippocampus, whereas in blood, C-JUN , NT5E , C-FOS , and ADORA1 were significantly downregulated. ADARB1 , NF-kB1 , MAPK1, C-FOS, and CREB1 showed the reverse direction of expressions in post-surgery blood samples. On clinico-genetic analysis, MAPK1 and ADARB1 correlated with neuronal dispersion in the dentate gyrus ( P = 0.02 and 0.03, respectively) and C-JUN correlated with neuronal loss in CA1 ( P = 0.01) and CA4 ( P = 0.04) areas. In blood, MAPK1 , NF-kB1 , and C-FOS expressions correlated negatively with the age of onset of seizures ( P = 0.02, 0.03, and 0.03, respectively). In addition, ADARB1 expression correlated with neuronal loss in CA3 and CA4 areas ( P ≤ 0.001 and 0.04, respectively).

Conclusion: Genes with similar expression patterns in the brain and peripheral blood are potential biomarkers in DRE-HS. Significant clinico-genetic correlations warrant further studies for developing novel therapeutic interventions.

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来源期刊
Annals of Indian Academy of Neurology
Annals of Indian Academy of Neurology Nervous System Diseases-
CiteScore
2.20
自引率
11.80%
发文量
293
审稿时长
29 weeks
期刊介绍: The journal has a clinical foundation and has been utilized most by clinical neurologists for improving the practice of neurology. While the focus is on neurology in India, the journal publishes manuscripts of high value from all parts of the world. Journal publishes reviews of various types, original articles, short communications, interesting images and case reports. The journal respects the scientific submission of its authors and believes in following an expeditious double-blind peer review process and endeavors to complete the review process within scheduled time frame. A significant effort from the author and the journal perhaps enables to strike an equilibrium to meet the professional expectations of the peers in the world of scientific publication. AIAN believes in safeguarding the privacy rights of human subjects. In order to comply with it, the journal instructs all authors when uploading the manuscript to also add the ethical clearance (human/animals)/ informed consent of subject in the manuscript. This applies to the study/case report that involves animal/human subjects/human specimens e.g. extracted tooth part/soft tissue for biopsy/in vitro analysis.
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