Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chonqing, China.
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chonqing, China.
CNS Neurosci Ther. 2020 Jan;26(1):101-116. doi: 10.1111/cns.13181. Epub 2019 Jun 9.
Semaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ-kindled epileptic rats.
First, we measured the Sema7A expression levels in patients with temporal lobe epilepsy (TLE) and in rats of a PTZ-kindled epilepsy rat model. Second, to explore the role of Sema7A in the regulation of seizure activity, we conducted epilepsy-related behavioral experiments after knockdown and overexpression of Sema7A in the rat hippocampal dentate gyrus (DG). Possible Sema7A-related brain immune regulators (eg, ERK phosphorylation, IL-6, and TNF-α) were also investigated. Additionally, the growth of mossy fibers was visualized by anterograde tracing using injections of biotinylated dextran amine (BDA) into the DG region.
Sema7A expression was markedly upregulated in the brain tissues of TLE patients and rats of the epileptic model after PTZ kindling. After knockdown of Sema7A, seizure activity was suppressed based on the latency to the first epileptic seizure, number of seizures, and duration of seizures. Conversely, overexpression of Sema7A promoted seizures. Overexpression of Sema7A increased the expression levels of the inflammatory cytokines, IL-6 and TNF-α, ERK phosphorylation, and growth of mossy fibers in PTZ-kindled epileptic rats.
Sema7A is upregulated in the epileptic brain and plays a potential role in the regulation of seizure activity in PTZ-kindled epileptic rats, which may be related to neuroinflammation. Sema7A promotes the inflammatory cytokines TNF-α and IL-6 as well as the growth of mossy fibers through the ERK pathway, suggesting that Sema7A may promote seizures by increasing neuroinflammation and activating pathological neural circuits. Sema7A plays a critical role in epilepsy and could be a potential therapeutic target for this neurological disorder.
信号素 7A（Sema7A）在大脑的免疫调节中发挥重要作用。在本研究中，我们旨在研究 Sema7A 在癫痫中的表达模式，并进一步探讨 Sema7A 在匹罗卡品诱导的癫痫大鼠中调节癫痫发作活动和炎症反应中的作用。
首先，我们测量了颞叶癫痫（TLE）患者和匹罗卡品诱导的癫痫大鼠模型中 Sema7A 的表达水平。其次，为了探讨 Sema7A 在调节癫痫发作活动中的作用，我们在大鼠海马齿状回（DG）中敲低和过表达 Sema7A 后进行了与癫痫相关的行为实验。还研究了可能与 Sema7A 相关的脑免疫调节剂（例如 ERK 磷酸化、IL-6 和 TNF-α）。此外，通过将生物素化葡聚糖胺（BDA）注入 DG 区域进行顺行追踪，可视化苔藓纤维的生长。
在 TLE 患者和匹罗卡品诱导的癫痫模型大鼠的脑组织中，Sema7A 的表达明显上调。敲低 Sema7A 后，根据首次癫痫发作的潜伏期、发作次数和发作持续时间，癫痫发作活动受到抑制。相反，过表达 Sema7A 则促进了癫痫发作。过表达 Sema7A 增加了炎性细胞因子 IL-6 和 TNF-α、ERK 磷酸化以及匹罗卡品诱导的癫痫大鼠苔藓纤维的生长。
Sema7A 在癫痫脑中上调，并在匹罗卡品诱导的癫痫大鼠中调节癫痫发作活动中发挥潜在作用，这可能与神经炎症有关。Sema7A 通过 ERK 途径促进炎性细胞因子 TNF-α和 IL-6 以及苔藓纤维的生长，表明 Sema7A 可能通过增加神经炎症和激活病理性神经回路来促进癫痫发作。Sema7A 在癫痫中起关键作用，可能成为这种神经障碍的潜在治疗靶点。
