Zubareva Olga E, Kovalenko Anna A, Kalemenev Sergey V, Schwarz Alexander P, Karyakin Vladimir B, Zaitsev Aleksey V
Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44 Toreza prospekt, Saint Petersburg 194223, Russia.
Federal State Budgetary Scientific Institution "Institute of Experimental Medicine", 12 Academician Pavlova Street, Saint Petersburg 197376, Russia.
Neurosci Lett. 2018 Nov 1;686:94-100. doi: 10.1016/j.neulet.2018.08.047. Epub 2018 Sep 3.
Temporal lobe epilepsy is the most prevalent form of complex partial seizure, and it is frequently triggered by an initial brain-damaging insult. The prevention of epileptogenesis after a primary event could be a key innovative approach to epilepsy treatment. Therefore, it is critical to understand the pathogenic mechanisms of this process in detail. Multiple mechanisms are involved in epileptogenesis, including alterations in the expression of synaptic receptors and transporters. The present study aimed to investigate the mRNA expression of excitatory amino acid transporters 1-3 (EAATs) and the subunits of the NMDA (GluN1, GluN2a, and GluN2b) and AMPA (GluA1 and GluA2) glutamate receptors following status epilepticus in a rat lithium-pilocarpine model. The analysis of the mRNA was performed via qRT-PCR one week after pilocarpine injections (the period of epileptogenesis) into the ventral and dorsal hippocampus and the entorhinal, temporal, and medial prefrontal cortexes - brain areas that are differentially involved in the pathogenesis of TLE. We found that increased EAAT2 mRNA levels in the medial prefrontal cortex and dorsal hippocampus may represent compensatory neuroprotective changes. Alterations in the gene expression levels of AMPA receptor subunits were found in the ventral hippocampus and temporal cortex. The reduced expression of the GluN2a subunit was observed in the temporal and entorhinal cortical areas and the ventral hippocampus, which may result in the predominance of GluN2b-containing NMDA receptors in these areas. The receptors with this altered subunit composition may be involved in pathophysiological mechanisms related to epileptogenesis. These data provide a better understanding of the pathogenesis of epilepsy.
颞叶癫痫是复杂部分性发作最常见的形式，且常由最初的脑损伤性损害引发。在原发性事件后预防癫痫发生可能是癫痫治疗的一种关键创新方法。因此，详细了解这一过程的致病机制至关重要。癫痫发生涉及多种机制，包括突触受体和转运体表达的改变。本研究旨在调查在大鼠匹罗卡品锂模型中癫痫持续状态后兴奋性氨基酸转运体1 - 3（EAATs）以及NMDA（GluN1、GluN2a和GluN2b）和AMPA（GluA1和GluA2）谷氨酸受体亚基的mRNA表达。在向腹侧和背侧海马以及内嗅、颞叶和内侧前额叶皮质（这些脑区在颞叶癫痫发病机制中所起作用不同）注射匹罗卡品（癫痫发生期）一周后，通过qRT - PCR对mRNA进行分析。我们发现内侧前额叶皮质和背侧海马中EAAT2 mRNA水平升高可能代表代偿性神经保护变化。在腹侧海马和颞叶皮质中发现了AMPA受体亚基基因表达水平的改变。在颞叶和内嗅皮质区域以及腹侧海马中观察到GluN2a亚基表达降低，这可能导致这些区域中含GluN2b的NMDA受体占主导。这种亚基组成改变的受体可能参与了与癫痫发生相关的病理生理机制。这些数据有助于更好地理解癫痫的发病机制。
