Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia
Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia
复制标题
局灶性皮质发育不良患者皮质病变中瞬时受体电位 Vanilloid 4 表达增加
DOI：
10.1111/cns.12494
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发表时间：
2016-04-01
影响因子：
5.5
通讯作者：
Yang, Hui
中科院分区：
文献类型：
--
作者：
Chen, Xin;Sun, Fei-Ji;Yang, Hui
局灶性皮质发育不良（FCD）是一种众所周知的难治性癫痫的原因。研究发现瞬时受体电位香草酸受体4（TRPV 4）可能参与癫痫发作的发生。本研究探讨了TRPV 4在FCD的表达模式和级联调节功能状态的TRPV 4在皮质neurons.MethodsThirty-nine FCD患者和10个年龄匹配的对照尸检标本的手术标本包括在这项研究中。Western blot、免疫组化和免疫荧光染色检测蛋白表达和分布。结果（1）FCD组TRPV 4蛋白水平及上游因子蛋白激酶C（PKC）蛋白水平均明显升高; (2)TRPV 4在FCD发育不良的皮质中染色较强，主要见于神经元微柱和畸形细胞。(3)TRPV 4的激活是[Ca 2 +]（i）升高皮质神经元的中心环节，其活性受PKC通路的调节，而不受PKA通路的调节。结论TRPV 4在FCD中的过表达和细胞分布的改变提示TRPV 4可能参与FCD的癫痫发生。
AimFocal cortical dysplasia (FCD) represents a well-known cause of medically intractable epilepsy. Studies found that transient receptor potential vanilloid receptor 4 (TRPV4) may participate in the occurrence of seizures. This study investigated the expression patterns of TRPV4 in FCD and the cascade that regulate functional state of TRPV4 in cortical neurons.MethodsThirty-nine surgical specimens from FCD patients and 10 age-matched control samples from autopsies were included in this study. Protein expression and distribution were detected by Western blot, immunohistochemistry, and immunofluorescence staining. Calcium imaging was used to detect the TRPV4-mediated Ca2+ influx in cortical neurons.Results(1) The protein levels of TRPV4 and of an upstream factor, protein kinase C (PKC), were markedly elevated in FCD. (2) TRPV4 staining was stronger in the dysplastic cortices of FCD and mainly observed in neuronal microcolumns and malformed cells. (3) The activation of TRPV4 was central for [Ca2+](i) elevation in cortical neurons, and this activity of TRPV4 in cortical neurons was regulated by the PKC, but not the PKA, pathway.ConclusionThe overexpression and altered cellular distribution of TRPV4 in FCD suggest that TRPV4 may potentially contribute to the epileptogenesis of FCD.