Upregulations of CRH and CRHR1 in the Epileptogenic Tissues of Patients with Intractable Infantile Spasms
Upregulations of CRH and CRHR1 in the Epileptogenic Tissues of Patients with Intractable Infantile Spasms
复制标题
顽固性婴儿痉挛症患者致癫痫组织中 CRH 和 CRHR1 的上调
DOI：
10.1111/cns.12598
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发表时间：
2017-01-01
影响因子：
5.5
通讯作者：
Liu, Shi-Yong
中科院分区：
文献类型：
--
作者：
Yang, Xiao-Lin;Chen, Bing;Liu, Shi-Yong
目的：婴儿痉挛症是一种年龄特异性癫痫综合征，具有特殊的临床症状和脑电图特征，缺乏治疗选择，预后不良。婴儿脑内内源性促肾上腺皮质激素释放激素（CRH）过多可能导致IS。然而，来自人类IS的数据是有限的。在我们的研究中，我们调查了CRH及其受体1型（CRHR1）在IS患者和尸检对照手术组织中的表达。方法：本研究包括17例IS患者的手术标本和6例尸检对照。采用实时荧光定量PCR、Western blotting、免疫组化等方法检测各组细胞的mRNA、蛋白表达及分布。变量间的相关性采用斯皮尔曼等级相关分析。结果：与对照组相比，IS患者致痫组织中CRH和CRHR 1的表达明显上调。CRH主要分布于神经元，CRHR1主要分布于神经元、星形胶质细胞和小胶质细胞。CRH和CRHR1的表达水平与癫痫发作频率呈正相关。此外，CRHR1的重要下游因子蛋白激酶C（PKC）在IS患者致痫组织中表达显著上调，且与CRHR1表达水平和癫痫痉挛频率呈正相关。结论：这些结果提示，CRH信号转导通路可能参与了IS的癫痫发生，支持CRH与IS发病机制有关的假说。
Aim: Infantile spasms (IS) are an age-specific epileptic syndrome with specific clinical symptom and electroencephalogram (EEG) features, lacking treatment options, and a poor prognosis. Excessive endogenous corticotropin-releasing hormone (CRH) in infant brain might result in IS. However, the data from human IS are limited. In our study, we investigated the expressions of CRH and its receptor type 1 (CRHR1) in surgical tissues from patients with IS and autopsy controls. Methods: Specimens surgically removed from 17 patients with IS, and six autopsy controls were included in the study. Real-time PCR, Western blotting, and immunostaining were used to detect the expressions of mRNA, protein expression, and distribution. The correlation between variates was analyzed by Spearman rank correlation. Results: The expressions of CRH and CRHR1 were significantly upregulated in the epileptogenic tissues of IS patients compared with the control group. CRH was distributed mainly in neurons, while CRHR1 was distributed in neurons, astrocytes, and microglia. The expression levels of CRH and CRHR1 were positively correlated with the frequency of epileptic spasms. Moreover, the expression of protein kinase C (PKC), which was an important downstream factor of CRHR1, was significantly upregulated in the epileptogenic tissues of patients with IS and was positively correlated with the CRHR1 expression levels and the frequency of epileptic spasms. Conclusion: These results suggest that the CRH signal transduction pathway might participate in the epileptogenesis of IS, supporting the hypothesis that CRH is related to the pathogenesis of IS.