Postnikova T Y, Zubareva O E, Kovalenko A A, Kim K K, Magazanik L G, Zaitsev A V
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia.
Biochemistry (Mosc). 2017 Mar;82(3):282-290. doi: 10.1134/S0006297917030063.
Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Real-time PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.
认知缺陷和记忆丧失在颞叶癫痫患者中很常见。突触效能的持续变化被认为是记忆过程的细胞基础。电生理研究表明，癫痫发作后，皮层和海马体中短期和长期突触可塑性的特性可能会发生显著变化。然而，导致这些变化的神经机制尚不清楚。在本研究中，我们调查了戊四氮（PTZ）诱导的癫痫持续状态24小时后大鼠海马切片中短期和长期突触可塑性的特性。我们发现，与对照组相比，CA1锥体细胞中长时程增强（LTP）的诱导减少，而短期易化增加。实验结果不支持癫痫持续状态导致海马突触背景增强，且由于重叠而使进一步的LTP诱导变弱这一假设，因为对照组和实验组动物中突触反应对输入刺激强度的依赖性并无差异。LTP的降低可能是由于神经元可塑性分子机制受损所致，包括与NMDA受体相关的机制和/或其亚基组成的变化。实时PCR显示，PTZ诱导的癫痫持续状态3小时后，GluN1和GluN2A亚基的表达显著增加。必需GluN1亚基的过表达表明海马体中NMDA受体总数增加。PTZ诱导的癫痫持续状态24小时后观察到GluN2B亚基的表达增加了3倍，这可能表明含GluN2B的NMDA受体比例增加。GluN2B亚基表达的增加可能是癫痫持续状态后海马突触处LTP幅度降低的一个原因。
