Ábrahám Hajnalka, Molnár Judit E, Sóki Noémi, Gyimesi Csilla, Horváth Zsolt, Janszky József, Dóczi Tamás, Seress László
Department of Medical Biology and Central Electron Microscopic Laboratory, University of Pécs Medical School, Szigeti u 12., Pécs 7624, Hungary.
Department of Medical Biology and Central Electron Microscopic Laboratory, University of Pécs Medical School, Szigeti u 12., Pécs 7624, Hungary.
Neuroscience. 2020 Nov 10;448:55-70. doi: 10.1016/j.neuroscience.2020.09.018. Epub 2020 Sep 12.
In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. Parvalbumin-immunoreactive cells were observed mostly in subgranular location in the dentate hilus in controls, in tumor-induced TLE, in malformation of cortical development and in MR-negative cases. In patients with HS, significant decrease in the number of hilar parvalbumin-immunoreactive cells and large numbers of ectopic parvalbumin-containing neurons were detected in the dentate gyrus' molecular layer. The ratio of ectopic/normally-located cells was significantly higher in HS than in other TLE groups. In patients with HS, robust sprouting of parvalbumin-immunoreactive axons were frequently visible in the molecular layer. The extent of sprouting was significantly higher in TLE patients with HS than in other groups. Strong sprouting of parvalbumin-immunoreactive axons were frequently observed in patients who had childhood febrile seizure. Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.
在本研究中，我们检查了不同病因的药物难治性颞叶癫痫（TLE）患者手术切除组织的齿状回中帕瓦丁免疫反应性细胞和轴突。根据MRI结果，将患者分为五组：（1）海马硬化（HS），（2）皮质发育畸形，（3）皮质发育畸形+HS，（4）肿瘤诱发的TLE，（5）MRI结果为阴性的患者。研究中还纳入了四个对照样本。在对照组、肿瘤诱发的TLE、皮质发育畸形和MRI阴性病例中，帕瓦丁免疫反应性细胞大多见于齿状回门区的颗粒下层。在HS患者中，门区帕瓦丁免疫反应性细胞数量显著减少，且在齿状回分子层检测到大量异位含帕瓦丁神经元。HS组异位/正常定位细胞的比例显著高于其他TLE组。在HS患者中，帕瓦丁免疫反应性轴突在分子层频繁出现强劲的发芽。HS的TLE患者轴突发芽程度显著高于其他组。在有儿童热性惊厥病史的患者中，经常观察到帕瓦丁免疫反应性轴突的强烈发芽。轴突发芽水平与异位/正常定位的含帕瓦丁细胞比例之间存在显著相关性。电子显微镜显示，发芽的帕瓦丁免疫反应性轴突终止于颗粒细胞近端和远端树突干以及树突棘上。我们的结果表明，HS中帕瓦丁免疫反应性神经元的靶标分布改变，这促成了TLE中已知的突触重塑。
