Nikbakht Farnaz, Hashemi Paria, Vazifekhah Somayeh, Babaei Javad Fahanik
Cellular and Molecular Research Center and Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Exp Brain Res. 2023 Mar;241(3):753-763. doi: 10.1007/s00221-023-06557-1. Epub 2023 Jan 31.
Clarifying the underlying mechanisms of epileptogenesis is important in preventing the progression of chronic epilepsy. In epilepsy, the mTOR (mammalian target of rapamycin) pathway plays a critical role in mediating the mechanism of epileptogenesis. In this study, we investigate whether apigenin can exert antiepileptogenic effects through the inhibition of mTOR in the kainate model of epilepsy. For assessing the antiepileptogenic effect of apigenin in kainic acid (KA)-induced temporal lobe epilepsy (TLE) model, apigenin at a dose of 50 mg/kg was administrated by gavage for 6 days. An intracranial electroencephalogram (iEEG) was performed to confirm the establishment of status epilepticus. BrdU was used to detect neurogenesis in the CA3, and dentate gyrus and mossy fiber sproutings were assessed by Timm staining. The expression of mTOR was quantified via western blot. We found that apigenin-pretreatment had a significant inhibitory effect on neural cell death, spontaneous seizure spikes, aberrant neurogenesis, mTOR hyperactivity, and aberrant mossy fiber sprouting. Overall, these results suggest that apigenin has an antiepileptogenic effect and may be a useful target for inhibiting mTOR hyperactivity in epilepsy.
阐明癫痫发生的潜在机制对于预防慢性癫痫的进展至关重要。在癫痫中，mTOR（雷帕霉素哺乳动物靶点）通路在介导癫痫发生机制中起关键作用。在本研究中，我们调查芹菜素是否能通过抑制红藻氨酸癫痫模型中的mTOR发挥抗癫痫发生作用。为评估芹菜素在红藻氨酸（KA）诱导的颞叶癫痫（TLE）模型中的抗癫痫发生作用，以50 mg/kg的剂量通过灌胃给予芹菜素，持续6天。进行颅内脑电图（iEEG）以确认癫痫持续状态的建立。使用溴脱氧尿苷（BrdU）检测CA3区的神经发生，并通过Timm染色评估齿状回和苔藓纤维出芽情况。通过蛋白质免疫印迹法对mTOR的表达进行定量分析。我们发现芹菜素预处理对神经细胞死亡、自发癫痫棘波、异常神经发生、mTOR过度激活和异常苔藓纤维出芽具有显著抑制作用。总体而言，这些结果表明芹菜素具有抗癫痫发生作用，可能是抑制癫痫中mTOR过度激活的有用靶点。
