PRG5 Knockout Precipitates Late-Onset Hypersusceptibility to Pilocarpine-Induced Juvenile Seizures by Exacerbating Hippocampal Zinc Signaling-Mediated Mitochondrial Damage.
PRG5 Knockout Precipitates Late-Onset Hypersusceptibility to Pilocarpine-Induced Juvenile Seizures by Exacerbating Hippocampal Zinc Signaling-Mediated Mitochondrial Damage.
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PRG5 敲除通过加剧海马锌信号介导的线粒体损伤而诱发对毛果芸香碱诱发的青少年癫痫发作的迟发性超敏性
DOI：
10.3389/fnins.2021.715555
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发表时间：
2021
影响因子：
4.3
通讯作者：
Ni H
中科院分区：
文献类型：
--
作者：
Wang D;Jin MF;Li L;Liu Y;Sun Y;Ni H
癫痫发生被理解为一种塑性过程，在潜伏期的突发性损伤（例如新生儿反复癫痫发作）后，大脑神经网络会产生持续的重组，最终导致神经元过度兴奋。可塑性相关基因（PRG），也称为脂质磷酸磷酸酶相关蛋白（PLPPR），是线粒体膜完整性和能量代谢的调节因子。本研究旨在确定PRG5基因敲除是否会导致发育性癫痫发作和海马苔藓纤维异常萌发引起的迟发型超敏反应，并确定其是否是通过线粒体途径实现的。在这里，我们通过将毛果芸香碱诱导的青少年癫痫发作与随后接触青霉素相结合，开发了一种“扭曲”癫痫发作模型，通过与野生型（WT）小鼠进行比较，测试 PRG5 敲除对癫痫发作潜伏期的长期影响。通过 Timm 染色检测海马苔藓纤维发芽（MFS）。为了阐明PRG5敲除引发的不良反应的机制，将海马HT22神经元培养物暴露于谷氨酸，有或没有PRG5干扰。检测线粒体功能、氧化应激指标和锌离子含量。 PRG5基因敲除显着降低了癫痫潜伏期，并加剧了发育性癫痫引起的癫痫阈值降低。此外，PRG5基因的敲除也在一定程度上降低了MFS评分。此外，PRG5基因沉默显着增加海马神经元中的锌离子含量，损害神经元活性和线粒体功能，并加剧谷氨酸诱导的氧化应激损伤。总之，与 WT 小鼠相比，PRG5 KO 与 PRG5(–/–) 小鼠对幼年癫痫发作的高度易感性显着相关。这些影响可能与海马锌信号传导有关。这些影响似乎与 MFS 的变化无关，因为患有青少年癫痫发作的 KO 小鼠的癫痫潜伏期最短，但表现出比患有青少年癫痫发作的 WT 小鼠更少的 MFS。
Epileptogenesis is understood as the plastic process that produces a persistent reorganization of the brain’s neural network after a precipitating injury (recurrent neonatal seizures, for instance) with a latent period, finally leading to neuronal hyperexcitability. Plasticity-related genes (PRGs), also known as lipid phosphate phosphatase-related proteins (PLPPRs), are regulators of mitochondrial membrane integrity and energy metabolism. This study was undertaken to determine whether PRG5 gene knockout contributes to the delayed hypersensitivity induced by developmental seizures and the aberrant sprouting of hippocampal mossy fibers, and to determine whether it is achieved through the mitochondrial pathway. Here, we developed a “twist” seizure model by coupling pilocarpine-induced juvenile seizures with later exposure to penicillin to test the long-term effects of PRG5 knockout on seizure latency through comparison with wild-type (WT) mice. Hippocampal mossy fiber sprouting (MFS) was detected by Timm staining. In order to clarify the mechanism of the adverse reactions triggered by PRG5 knockout, hippocampal HT22 neuronal cultures were exposed to glutamate, with or without PRG5 interference. Mitochondrial function, oxidative stress indicators and zinc ion content were detected. PRG5 gene knockout significantly reduced the seizure latency, and aggravated the lowered seizure threshold induced by developmental seizures. Besides, knockout of the PRG5 gene reduced the MFS scores to a certain extent. Furthermore, PRG5 gene silencing significantly increases the zinc ion content in hippocampal neurons, impairs neuronal activity and mitochondrial function, and exacerbates glutamate-induced oxidative stress damage. In summary, PRG5 KO is associated with significantly greater hypersusceptibility to juvenile seizures in PRG5(–/–) mice compared with WT mice. These effects may be related to the hippocampal zinc signaling. The effects do not appear to be related to changes in MFS because KO mice with juvenile seizures had the shortest seizure latencies but exhibited less MFS than WT mice with juvenile seizures.
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DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ
影响因子：
2.7
作者：
Song, Ji Hoon;Kang, Ki Sung;Choi, You-Kyung
通讯作者：
Choi, You-Kyung
影响因子：
5.4
作者：
Companys-Alemany, Julia;Turcu, Andreea L.;Grinan-Ferre, Christian
通讯作者：
Grinan-Ferre, Christian
生酮饮食野生型大鼠的神经行为状态和海马代谢相关基因的表达
影响因子：
3.4
作者：
Ling, Ya;Wang, Dan-dan;Ni, Hong
通讯作者：
Ni, Hong
影响因子：
2.1
作者：
Malaga, Ignacio;Sanchez-Carpintero, Rocio;Jose Garcia-Penas, Juan
通讯作者：
Jose Garcia-Penas, Juan