Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus
Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus
复制标题
DOI：
10.1016/j.brainres.2009.05.066
复制
发表时间：
2009-08-04
期刊：
影响因子：
2.9
通讯作者：
Churn, Severn B.
中科院分区：
文献类型：
--
作者：
Bracey, James M.;Kurz, Jonathan E.;Churn, Severn B.
癫痫持续状态是一种危及生命的癫痫发作形式，是一种与显着发病率和死亡率相关的重大医疗紧急情况。蛋白激酶 A 是突触强度的重要调节剂，可能在癫痫持续状态诱发的神经元病理学的发展中发挥重要作用。这项研究表明，在 SE 后期，针对外源和内源底物的 PKA 活性有所增加。随着 SE 的进展，皮层结构中 PKA 介导的外源肽底物磷酸化显着增加。活性的增加并不是由于酶的调节亚基或催化亚基的表达改变所致。通过使用磷酸化特异性抗体，本研究还研究了 SE 对谷氨酸受体 AMPA 亚型的 GluR1 亚基磷酸化的影响。持续癫痫发作后，观察到 AMPA 受体 GluR1 亚基上 PKA 位点的磷酸化增加。这些数据表明 SE 可能增加皮质神经元兴奋性的潜在机制，可能导致癫痫活动或长期神经元病理的维持。 (C) 2009 Elsevier B.V. 保留所有权利。
Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology. (C) 2009 Elsevier B.V. All rights reserved.