Department of Biomedical Sciences, College of Life Science, Hallym University, Chunchon Kangwon-Do 200-702, Republic of Korea.
BMC Neurosci. 2010 Oct 28;11:141. doi: 10.1186/1471-2202-11-141.
In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.
Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.
Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.
为了确定肌酸（Cr）在癫痫中的作用，我们研究了 Cr、肌酸转运蛋白（CRT）和肌酸激酶（CKs）对化学诱导的急性癫痫发作和慢性癫痫发作活动的抗惊厥作用。
在匹罗卡品（PILO）-癫痫发作诱导后 2 小时，与对照水平相比，普遍存在的线粒体 CK（uMtCK）免疫反应性没有改变。然而，脑型细胞质 CK（BCK）免疫反应性下降到对照水平的 70%。CRT 免疫反应性下降到对照水平的 60%。在 Cr 或 Tat-CK 治疗后，uMtCK 或 CRT 免疫反应性不受影响，而 Cr 处理组的 BCK 免疫反应性增加到对照水平的 3.6 倍。β-胍基丙酸（GPA，一种竞争性 CRT 抑制剂）降低了 BCK 和 CRT 的表达。此外，Cr 和 tat-BCK 治疗延迟了 PILO 注射后癫痫发作活动的开始。然而，GPA 治疗在没有 PILO 治疗的情况下诱导自发性癫痫发作。在慢性癫痫大鼠中，海马中的 uMtCK 和 CRT 免疫反应性均降低。相比之下，BCK 免疫反应性与对照动物相似。Cr、GPA 和 tat-BCK 治疗不能改变 EEG。
Cr/CK 循环可能在维持或加剧急性癫痫发作活动中起重要作用，但在慢性癫痫放电中不起作用。
