Department of Biophysics, AIIMS, New Delhi, India.
Department of Neurosurgery, AIIMS, New Delhi, India.
Neurosci Lett. 2021 Sep 14;761:136096. doi: 10.1016/j.neulet.2021.136096. Epub 2021 Jul 1.
Mesial temporal lobe epilepsy with hippocamapal sclerosis (MTLE-HS) is the most common form of drug resistant epilepsy (DRE). MTLE-HS is a distributed network disorder comprising of not only the hippocampus, but other anatomically related extrahippocampal regions. Excitatory synaptic transmission is differentially regulated in the hippocampal and extra-hippocampal regions of patients with MTLE-HS, but its mechanism not understood. Cyclin-dependent kinase 5 (Cdk5) is known to regulate synaptic transmission and plasticity through up-regulation of NMDA receptors by phosphorylating NR2Asubunits. The present study is designed to investigate whether Cdk5 differentially regulates the excitatory synaptic transmission in the hippocampus and anterior temporal lobe (ATL) samples obtained from patients of MTLE-HS. We have measured the Cdk5 kinase activity and the protein levels of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the hippocampal and ATL samples obtained from patients with MTLE-HS. We have also determined the effect of roscovitine, a Cdk5 antagonist, on spontaneous excitatory postsynaptic currents (EPSCs) recorded from the hippocampal and ATL using patch-clamp technique. We observed significant increase in the expression of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the ATL samples as compared to the hippocampal samples. Cdk5 activity was significantly higher in ATL samples as compared to the hippocampal samples. Magnitude of reduction in the frequency of EPSCs by roscovitine in the ATL samples was higher than that in the hippocampal samples. Our studies suggest that Cdk5 differentially regulates excitatory synaptic activity in the hippocampal and ATL region of patients with MTLE-HS.
内侧颞叶癫痫伴海马硬化（MTLE-HS）是最常见的耐药性癫痫（DRE）形式。MTLE-HS 是一种分布式网络障碍，不仅包括海马体，还包括其他解剖上相关的海马外区域。在 MTLE-HS 患者的海马和海马外区域，兴奋性突触传递被不同程度地调节，但其机制尚不清楚。周期蛋白依赖性激酶 5（Cdk5）通过磷酸化 NR2A 亚基上调 NMDA 受体，已知可调节突触传递和可塑性。本研究旨在探讨 Cdk5 是否在从 MTLE-HS 患者获得的海马和前颞叶（ATL）样本中差异调节兴奋性突触传递。我们已经测量了从 MTLE-HS 患者获得的海马和 ATL 样本中 Cdk5 激酶活性和 Cdk5、p-Cdk5、p35/p25、NR2A、pNR2A 的蛋白水平。我们还使用膜片钳技术确定了 Cdk5 拮抗剂罗昔洛韦对从海马和 ATL 记录的自发兴奋性突触后电流（EPSC）的影响。与海马体样本相比，我们观察到 ATL 样本中 Cdk5、p-Cdk5、p35/p25、NR2A、pNR2A 的表达显著增加。与海马体样本相比，ATL 样本中的 Cdk5 活性显著升高。罗昔洛韦对 ATL 样本中 EPSC 频率的降低幅度高于海马体样本。我们的研究表明，Cdk5 可在 MTLE-HS 患者的海马和 ATL 区域差异调节兴奋性突触活性。
