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长链非编码 RNA 的作用;BDNF-AS 和 17A 及其与埃及癫痫患者 GABA 能功能障碍的关系。

Role of long noncoding RNAs; BDNF-AS and 17A and their relation to GABAergic dysfunction in Egyptian epileptic patients.

机构信息

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt.

Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

出版信息

Metab Brain Dis. 2023 Apr;38(4):1193-1204. doi: 10.1007/s11011-023-01182-x. Epub 2023 Feb 20.

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures. Lately, long noncoding RNAs (lncRNAs) have been increasingly appreciated as regulators of epilepsy-related processes, however, their functional role in its pathogenesis is still to be explored. This study investigated the expression levels of lncRNAs; BDNF-AS and 17A in the sera of Egyptian patients with idiopathic generalized and symptomatic focal epilepsy and correlated their levels with brain-derived neurotrophic factor (BDNF), phosphorylated cAMP reaction element -binding protein (p-CREB), gamma- aminobutyric acid (GABA) and glutamate, to underline their related molecular mechanism. A total of 70 epileptic patients were divided into two clinical types, besides 30 healthy controls of matched age and sex. The expression levels of both lncRNAs were markedly upregulated in epileptic groups versus the healthy control group with predominance in the symptomatic focal one. Epileptic patients showed significantly lower levels of BDNF, p-CREB, GABA along with significant increase of glutamate levels and glutamate/ GABA ratio, especially in symptomatic focal versus idiopathic generalized epileptic ones. The obtained data raised the possibility that these lncRNAs might be involved in the pathogenesis of epilepsy via inhibition of GABA/p-CREB/BDNF pathway. The study shed light on the putative role of these lncRNAs in better diagnosis of epilepsy, particularly symptomatic focal epilepsy.

摘要

癫痫是一种以反复发作、无诱因癫痫发作为特征的慢性神经系统疾病。最近,长链非编码 RNA(lncRNA)被越来越多地认为是调节癫痫相关过程的因素,然而,它们在发病机制中的功能作用仍有待探索。本研究调查了 lncRNA;BDNF-AS 和 17A 在埃及特发性全面性和症状性局灶性癫痫患者血清中的表达水平,并将其水平与脑源性神经营养因子(BDNF)、磷酸化环磷腺苷反应元件结合蛋白(p-CREB)、γ-氨基丁酸(GABA)和谷氨酸相关联,以强调它们的相关分子机制。总共 70 名癫痫患者分为两种临床类型,此外还有 30 名年龄和性别匹配的健康对照组。两种 lncRNA 的表达水平在癫痫组明显高于健康对照组,在症状性局灶性癫痫组更为明显。癫痫患者的 BDNF、p-CREB、GABA 水平明显降低,谷氨酸水平明显升高,谷氨酸/ GABA 比值明显升高,特别是在症状性局灶性癫痫组与特发性全面性癫痫组之间。这些数据表明,这些 lncRNA 可能通过抑制 GABA/p-CREB/BDNF 通路参与癫痫的发病机制。该研究阐明了这些 lncRNA 在癫痫,特别是症状性局灶性癫痫的更好诊断中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9a/10110666/05610c1c8b9f/11011_2023_1182_Fig1_HTML.jpg

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