The Functional State of Glutamate- and GABA-Ergic Neurons in the Inferior Colliculi of Krushinsky–Molodkina Rats at Early Stages of Epileptogenesis

IF 0.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
S. D. Nikolaeva, L. S. Nikitina, M. V. Glazova, V. T. Bakhteeva, E. V. Chernigovskaya
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Abstract

Disturbances in the neurotransmitter systems associated with the development of temporal lobe epilepsy (TLE) have been well-studied in forebrain structures including the temporal cortex, amygdala, and hippocampus. It is known that in rodents genetically prone to audiogenic seizures, TLE establishment induced by audiogenic kindling is also associated with the involvement of the forebrain, however, initially epileptiform activity arises in the brainstem, in particular, in the inferior colliculi (IC). It is reasonable to suppose that neurochemical alterations in the IC may contribute significantly to the spreading of epileptiform activity at early steps of TLE development. At the same time, the functional state of the key neurotransmitter systems in the IC of audiogenic rodents exposed to audiogenic kindling remains unknown. In the present work, we performed a comprehensive analysis of proteins involved in glutamate- and GABA-ergic transmission in the IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures. A modified audiogenic kindling protocol was used to reproduce the early stage of TLE development. According to this protocol, rats were exposed to daily audiogenic stimulations for seven days. Naive KM rats were used as a control. Although the rodent’s predisposition to audiogenic seizures is often associated with the impairment of GABAergic transmission, no significant changes were found in the expression of GABA synthesis enzymes and GABAA receptor α1 subunit in the IC of KM rats either 24 hours or a week after their last seizure. However, 24 hours after the last audiogenic stimulation, an increase in glutamatergic transmission in the IC was observed including upregulation of ERK 1/2 kinases, synaptic proteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week after the last seizure, only an increase in VGLUT1 content in the IC was observed, suggesting the persistent changes in the neurons of forebrain structures, in particular, of the temporal cortex.

Abstract Image

癫痫发生早期克鲁辛斯基-莫洛金娜大鼠下丘脑谷氨酸能神经元和 GABA 能神经元的功能状态
摘要与颞叶癫痫(TLE)发病有关的神经递质系统紊乱已在前脑结构中得到了深入研究,包括颞皮层、杏仁核和海马体。然而,最初的痫样活动出现在脑干,尤其是下侧副神经体(IC)。我们有理由推测,在 TLE 发病的早期阶段,IC 内的神经化学变化可能在很大程度上导致了癫痫样活动的扩散。与此同时,暴露于发声性点燃的发声啮齿动物的集成电路中关键神经递质系统的功能状态仍然未知。在本研究中,我们对易患听源性癫痫的遗传大鼠克鲁辛斯基-莫洛金娜(KM)的集成电路中参与谷氨酸和GABA能传导的蛋白质进行了全面分析。为了重现TLE发展的早期阶段,我们使用了一种改良的致听性点燃方案。根据该方案,大鼠每天受到致听刺激,持续七天。虽然啮齿动物的致听性癫痫发作倾向通常与 GABAergict 传递受损有关,但在 KM 大鼠最后一次癫痫发作 24 小时后或一周后,其 IC 中 GABA 合成酶和 GABAA 受体α1 亚基的表达均未发现明显变化。然而,在最后一次致听刺激 24 小时后,在 IC 中观察到谷氨酸能传导的增加,包括 ERK 1/2 激酶、突触蛋白突触素 1 和 SV2B、VGLUT1 和 VGLUT2 的上调。在最后一次癫痫发作一周后,只观察到集成电路中 VGLUT1 的含量增加,这表明前脑结构的神经元,尤其是颞叶皮层的神经元发生了持续变化。
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来源期刊
自引率
33.30%
发文量
110
审稿时长
6-12 weeks
期刊介绍: Journal of Evolutionary Biochemistry and Physiology  publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
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