Histone deacetylases (HDACs) have been described to have both neurotoxic and neuroprotective roles, and partly, depend on its sub-cellular distribution. HDAC inhibitors have a long history of use in the treatment of various neurological disorders including epilepsy. Key role of HDACs in GABAergic neurotransmission, synaptogenesis, synaptic plasticity and memory formation was demonstrated whereas very less is known about their role in drug-resistant epilepsy pathologies. The present study was aimed to investigate the changes in the expression of HDACs, activity and its sub-cellular distribution in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. For this study, surgically resected hippocampal tissue specimens of 28 MTLE-HS patients and 20 hippocampus from post-mortem cases were obtained. Real-time PCR was done to analyse the mRNA expression. HDAC activity and the protein levels of HDACs in cytoplasm as well as nucleus were measured spectrophotometrically. Further, sub-cellular localization of HDACs was characterized by immunofluorescence. Significant upregulation of HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC10 and HDAC11 mRNA were observed in MTLE-HS. Alterations in the mRNA expression of glutamate and gamma-aminobutyric acid (GABA) receptor subunits have been also demonstrated. We observed significant increase of HDAC activity and nuclear level of HDAC1, HDAC2, HDAC5 and HDAC11 in the hippocampal samples obtained from patients with MTLE-HS. Moreover, we found altered cytoplasmic level of HDAC4, HDAC6 and HDAC10 in the hippocampal sample obtained from patients with MTLE-HS. Alterations in the level of HDACs could potentially be part of a dynamic transcription regulation associated with MTLE-HS. Changes in cytoplasmic level of HDAC4, 6 and 10 suggest that cytoplasmic substrates may play a crucial role in the pathophysiology of MTLE-HS. Knowledge regarding expression pattern and sub-cellular distribution of HDACs may help to devise specific HDACi therapy for epilepsy.

组蛋白脱乙酰酶 (HDAC) 已被描述为具有神经毒性和神经保护作用，并且部分取决于其亚细胞分布。HDAC抑制剂在治疗包括癫痫在内的各种神经系统疾病方面有着悠久的历史。HDAC 在 GABA 能神经传递、突触发生、突触可塑性和记忆形成中的关键作用得到了证实，而人们对其在耐药性癫痫病理中的作用知之甚少。本研究旨在探讨HDACs表达、活性及其亚细胞分布在颞叶内侧癫痫伴海马硬化（MTLE-HS）患者中的变化。在这项研究中，获得了 28 名 MTLE-HS 患者和 20 名死后海马的手术切除海马组织标本。进行实时PCR以分析mRNA表达。用分光光度法测量HDAC活性和细胞质和细胞核中HDAC的蛋白质水平。此外，HDAC 的亚细胞定位以免疫荧光为特征。在 MTLE-HS 中观察到 HDAC1、HDAC2、HDAC4、HDAC5、HDAC6、HDAC10 和 HDAC11 mRNA 的显着上调。谷氨酸和 γ-氨基丁酸 (GABA) 受体亚基的 mRNA 表达的改变也已得到证实。我们观察到从 MTLE-HS 患者获得的海马样本中 HDAC 活性和 HDAC1、HDAC2、HDAC5 和 HDAC11 的核水平显着增加。此外，我们发现从 MTLE-HS 患者获得的海马样本中 HDAC4、HDAC6 和 HDAC10 的细胞质水平发生了改变。HDAC 水平的改变可能是与 MTLE-HS 相关的动态转录调控的一部分。HDAC4、6和10细胞质水平的变化表明细胞质底物可能在MTLE-HS的病理生理学中起关键作用。关于 HDAC 的表达模式和亚细胞分布的知识可能有助于设计针对癫痫的特定 HDACi 疗法。