Open AccessUpregulations of CRH and CRHR 1 in the Epileptogenic Tissues of Patients with Intractable Infantile Spasms
Author(s) -
Yang XiaoLin,
Chen Bing,
Zhang XiaoQing,
Chen Xin,
Yang MeiHua,
Zhang Wei,
Chen HuanRan,
Zang ZhenLe,
Li Wei,
Yang Hui,
Liu ShiYong
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12598
Subject(s) - epileptogenesis , immunostaining , blot , medicine , pathogenesis , downregulation and upregulation , immunohistochemistry , neuroscience , endocrinology , biology , hippocampus , gene , biochemistry
Summary 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 ( CRHR 1) 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 CRHR 1 were significantly upregulated in the epileptogenic tissues of IS patients compared with the control group. CRH was distributed mainly in neurons, while CRHR 1 was distributed in neurons, astrocytes, and microglia. The expression levels of CRH and CRHR 1 were positively correlated with the frequency of epileptic spasms. Moreover, the expression of protein kinase C ( PKC ), which was an important downstream factor of CRHR 1, was significantly upregulated in the epileptogenic tissues of patients with IS and was positively correlated with the CRHR 1 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 .