A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.
A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.
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大鼠齿状回谷氨酰胺合成酶的短暂上调参与杏仁核点燃诱导的癫痫发生
DOI：
10.1371/journal.pone.0066885
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Sun HL;Zhang SH;Zhong K;Xu ZH;Feng B;Yu J;Fang Q;Wang S;Wu DC;Zhang JM;Chen Z
谷氨酰胺合成酶（GS）功能的降低与癫痫的发生密切相关，但其在癫痫发生中的作用却知之甚少。本研究旨在通过电刺激基底外侧杏仁核诱发大鼠杏仁核点燃癫痫模型，探讨GS在脑内的功能变化及其在癫痫发生中的作用。当点燃癫痫发作进展到第4期时，同侧齿状回（DG）中GS的表达和活性均上调。在第一次3阶段癫痫发作后第3天（就在GS上调之前），将单剂量的L-甲硫氨酸亚砜亚胺（MSO，2 μl）（一种选择性GS抑制剂）给予同侧DG。研究发现，低剂量MSO（5或10 µg）可显著降低诱发性癫痫发作的严重程度和易感性，且呈剂量依赖性，而高剂量（20 µg）MSO可加重点燃性癫痫发作。在使用10 µg MSO成功抑制癫痫发作的动物中，当癫痫发作再次进展至4期时，再次发生GS上调，再次给予10 µg MSO可持续降低癫痫发作。1.5 µg剂量的GLN可消除10 µg MSO对点燃癫痫发作的抑制作用和20 µg MSO对点燃癫痫发作的有害作用。此外，适当的人工microRNA干扰（1和1.5×106 TU/2 μl）同侧DG中的GS表达也抑制了癫痫发作的进展。此外，在戊四氮点燃诱发的癫痫发生过程中，也观察到皮层GS表达和活性的短暂增加。这些结果有力地表明，GS功能的瞬时和区域特异性上调发生时，癫痫发展到一定阶段，并最终促进癫痫发生的过程。在适当的时间和适当的程度上抑制GS可能是中断癫痫发生的潜在治疗方法。
Reduction of glutamine synthetase (GS) function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG) were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl), a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated). It was found that low doses of MSO (5 or 10 µg) significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg) aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×106 TU/2 µl) of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.
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影响因子：
5.5
作者：
Hu, Wei-Wei;Fang, Qi;Chen, Zhong
通讯作者：
Chen, Zhong
影响因子：
6.2
作者：
Kang, Tae-Cheon;Kim, Duk-Soo;Kwon, Oh-Shin
通讯作者：
Kwon, Oh-Shin
影响因子：
2.9
作者：
HAMBERGER, AC;CHIANG, GH;COTMAN, CW
通讯作者：
COTMAN, CW
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：
5.6
作者：
Bidmon, Hans-J;Goerg, Boris;Zilles, Karl
通讯作者：
Zilles, Karl