Convulsive responses to seizure-inducible drugs are exacerbated in progranulin-deficient mice
Convulsive responses to seizure-inducible drugs are exacerbated in progranulin-deficient mice
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颗粒体蛋白前体缺陷小鼠对癫痫诱导药物的惊厥反应加剧
DOI：
10.1097/wnr.0000000000001425
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发表时间：
2020
期刊：
影响因子：
1.7
通讯作者：
Nishihara M
中科院分区：
文献类型：
--
作者：
Kuroda M;Matsuwaki T;Tanaka Y;Yamanouchi K;Nishihara M
颗粒蛋白前体（PGRN）是一种广泛表达于包括中枢神经系统在内的器官中的糖蛋白。PGRN不足涉及各种神经退行性疾病，如额颞叶痴呆、阿尔茨海默病和神经元蜡样脂褐质沉积症。神经元损伤的主要原因之一是由兴奋系统的上调触发的大脑的过度激活。在本研究中，我们研究了可能参与PGRN在调制的大脑兴奋性使用野生型和PGRN缺陷小鼠。首先，我们用可诱导神经元兴奋的药物荷包牡丹碱或N-甲基-D-天冬氨酸（NMDA）治疗野生型和PGRN缺陷型小鼠。PGRN缺陷小鼠表现出更高的癫痫发作强度和惊厥行为的持续时间较长时，无论是荷包牡丹碱或NMDA治疗。接下来，我们定量海马和大脑皮层中NMDA受体亚单位的表达。NR 2A亚基蛋白在PGRN缺陷小鼠海马中的表达水平显著升高，而在大脑皮层中没有观察到差异。另一方面，海马中NMDA受体亚基的mRNA水平与PGRN缺陷小鼠相当，甚至更低。这些结果表明，PGRN调节大脑的兴奋性，至少部分地调节海马中的NMDA受体的蛋白质水平。
Progranulin (PGRN) is a glycoprotein that is widely expressed among organs, including the central nervous system. PGRN insufficiency is involved in various neurodegenerative disorders such as frontotemporal dementia, Alzheimer’s disease, and neuronal ceroid lipofuscinosis. One of the major causes of neuronal damage is hyperactivation of the cerebrum triggered by upregulation of excitatory systems. In the present study, we examined the possible involvement of PGRN in modulating excitability of the cerebrum using wild type and PGRN-deficient mice. First, we treated wild type and PGRN-deficient mice with seizure-inducible drugs, bicuculline or N-methyl-D-aspartate (NMDA), which provoke hyperexcitement of neurons. PGRN-deficient mice showed higher intensity of seizure and longer duration of convulsive behavior when treated with either bicuculline or NMDA. Next, we quantified the expression of NMDA receptor subunits in the hippocampus and cerebral cortex. The expression level of NR2A subunit protein was significantly higher in the hippocampus of PGRN-deficient mice, while no difference was observed in the cerebral cortex. On the other hand, mRNA levels of NMDA receptor subunits in the hippocampus were comparable or even lower in PGRN-deficient mice. These results suggest that PGRN modulates the excitability of the cerebrum by regulating at least partially the protein level of NMDA receptors in the hippocampus.
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化学诱发的急性癫痫发作和癫痫模型：有毒化合物和成瘾药物
DOI：
--
发表时间：
2017
期刊：
影响因子：
--
作者：
F. Dorandeu;G. Calas;G. Bo;R. Fares
通讯作者：
R. Fares
阿尔茨海默病中的谷氨酸和其他脑脊液氨基酸。
DOI：
10.1176/ajp.149.2.251
发表时间：
1992
期刊：
The American journal of psychiatry
影响因子：
--
作者：
N. Pomara;Rajkumar Singh;D. Deptula;J. Chou;Miriam Banay Schwartz;P. LeWitt
通讯作者：
P. LeWitt
颗粒体蛋白前体突变影响额颞叶痴呆的大脑振荡活动
影响因子：
4.8
作者：
D. Moretti;L. Benussi;Silvia Fostinelli;M. Ciani;G. Binetti;R. Ghidoni
通讯作者：
R. Ghidoni
促生蛋白突变是阿尔茨海默氏病的危险因素。
影响因子：
29
作者：
Perry, David C.;Lehmann, Manja;Yokoyama, Jennifer S.;Karydas, Anna;Lee, Jason JiYong;Coppola, Giovanni;Grinberg, Lea T.;Geschwind, Dan;Seeley, William W.;Miller, Bruce L.;Rosen, Howard;Rabinovici, Gil
通讯作者：
Rabinovici, Gil
影响因子：
2.9
作者：
Guo, Aobo;Tapia, Lucia;Jia, William
通讯作者：
Jia, William