Department of Pediatrics, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, 134 East Street, Gulou District, Fuzhou, 350001, Fujian Province, China.
Department of clinical medicine, Fujian Medical University, Fuzhou, 350001, Fujian Province, China.
Metab Brain Dis. 2023 Feb;38(2):453-466. doi: 10.1007/s11011-022-01077-3. Epub 2022 Sep 12.
Maintaining the balance of mitochondrial fission and mitochondrial autophagy on seizures is helpful to find a solution to control seizures and reduce brain injuries. The present study is to investigate the protective effect of inhibiting mitochondrial fission on brain injury in juvenile rat epilepsy induced by pentatetrazol (PTZ) by inhibiting the BCL2L13/LC3-mediated mitophagy pathway. PTZ was injected (40 mg/kg) to induce kindling once every other day, for a total of 15 times. In the PTZ + DMSO (DMSO), PTZ + Mdivi-1 (Mdivi-1), and PTZ + WY14643 (WY14643) groups, rats were pretreated with DMSO, Mdivi-1 and WY14643 for half an hour prior to PTZ injection. The seizure attacks of young rats were observed for 30 min after model establishment. The Morris water maze (MWM) was used to test the cognition of experimental rats. After the test, the numbers of NeuN(+) neurons and GFAP(+) astrocytes were observed and counted by immunofluorescence (IF). The protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampus of young rats were detected by immunohistochemistry (IHC) and Western blotting (WB). Compared with the PTZ and DMSO groups, the seizure latency in the Mdivi-1 group was longer (P < 0.01), and the severity degree and frequency of seizures were lower (P < 0.01). The MWM test showed that the incubation periods of crossing the platform in the Mdivi-1 group was significantly shorter. The number of platform crossings, the platform stay time, and the ratio of residence time/total stay time were significantly increased in the Mdivi-1 group (P < 0.01). The IF results showed that the number of NeuN(+) neurons in the Mdivi-1 group was greater, while the number of GFAP(+) astrocytes was lower. IHC and WB showed that the average optical density (AOD) and relative protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampi of rats in the Mdivi-1 group were higher (P < 0.05). The above results in the WY14643 group were opposite to those in the Mdivi-1 group. Inhibition of mitochondrial fission could reduce seizure attacks, protect injured neurons, and improve cognition following PTZ-induced epilepsy by inhibiting mitochondrial autophagy mediated by the BCL2L13/LC3 mitophagy pathway.
维持线粒体裂变和线粒体自噬在癫痫发作中的平衡有助于找到控制癫痫发作和减少脑损伤的解决方案。本研究旨在通过抑制 BCL2L13/LC3 介导的线粒体自噬通路，研究抑制线粒体裂变对戊四氮（PTZ）诱导的幼年大鼠癫痫发作后脑损伤的保护作用。PTZ（40mg/kg）每隔一天注射一次以诱导点燃，共 15 次。在 PTZ+DMSO（DMSO）、PTZ+Mdivi-1（Mdivi-1）和 PTZ+WY14643（WY14643）组中，大鼠在注射 PTZ 前半小时预先用 DMSO、Mdivi-1 和 WY14643 处理。模型建立后，观察幼鼠 30min 的癫痫发作攻击。使用 Morris 水迷宫（MWM）测试实验大鼠的认知能力。测试后，通过免疫荧光（IF）观察和计数幼鼠海马区 NeuN（+）神经元和 GFAP（+）星形胶质细胞的数量。通过免疫组织化学（IHC）和 Western blot（WB）检测幼鼠海马区 Drp1、BCL2L13、LC3 和 caspase 3 的蛋白表达水平。与 PTZ 和 DMSO 组相比，Mdivi-1 组的癫痫发作潜伏期更长（P<0.01），癫痫发作的严重程度和频率更低（P<0.01）。MWM 测试表明，Mdivi-1 组穿过平台的潜伏期明显缩短。Mdivi-1 组平台穿越次数、平台停留时间和停留时间/总停留时间的比例明显增加（P<0.01）。IF 结果显示，Mdivi-1 组的 NeuN（+）神经元数量较多，而 GFAP（+）星形胶质细胞数量较少。IHC 和 WB 显示，Mdivi-1 组大鼠海马区 Drp1、BCL2L13、LC3 和 caspase 3 的平均光密度（AOD）和相对蛋白表达水平均升高（P<0.05）。WY14643 组的上述结果与 Mdivi-1 组相反。抑制线粒体裂变可通过抑制 BCL2L13/LC3 介导的线粒体自噬，减少 PTZ 诱导的癫痫发作后的癫痫发作、保护受损神经元和改善认知。
Eur Rev Med Pharmacol Sci. 2014
Free Radic Biol Med. 2016-5
Pharmacol Biochem Behav. 2014-5
CNS Neurosci Ther. 2025-1
CNS Neurosci Ther. 2024-10
Mil Med Res. 2024-5-29
Zotero 插件