The Effect of Pyridine Oxime Derivative (GIZh-298) and Sodium Valproate on the Neurotransmitter Amino Acids Content in the Brain Structures of Mice in the Maximal Electroshock Seizure Test

IF 0.5 4区医学 Q4 NEUROSCIENCES Neurochemical Journal Pub Date : 2024-05-27 DOI:10.1134/s1819712424020107

V. B. Narkevich, S. A. Litvinova, K. A. Kasabov, A. A. Yakovleva, V. S. Kudrin, T. A. Voronina

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Abstract—Here we studied the effects of anti-epileptic substance GIZh-298 and the drug of comparison sodium valproate (NaV) on the contents of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the mouse brain in a model of generalized tonic-clonic seizures induced by maximal electroshock (MES). The levels of excitatory amino acids such as aspartate in the hypothalamus and glutamate in the hippocampus were decreased by 20.8 and 16.7%, respectively, and of inhibitory amino acids, such as glycine, GABA, and taurine were also decreased by 16–20% in average in those structures 5 min after the MES application indicating the exhaustion of aminoacidic neurotransmission. Intragastric administration of NaV at a dose of 200 mg/kg, which causes the anti-seizure effect, prevented the MES-induced decrease in the content of GABA and the GABA/glutamate ratio in the hypothalamus. NaV similarly decreased the aspartate level in the hypothalamus, striatum, and hippocampus in the intact group of mice and in mice after seizures. Intragastric administration of GIZh-298 at a dose of 60 mg/kg prevented the MES-evoked decrease in the GABA/glutamate ratio and the levels of GABA, glycine, and taurine in the hypothalamus.

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吡啶肟衍生物（GIZh-298）和丙戊酸钠对最大电击癫痫发作试验中小鼠脑结构中神经递质氨基酸含量的影响

摘要--我们研究了抗癫痫物质GIZh-298和对比药物丙戊酸钠（NaV）对最大电休克（MES）诱导的全身强直-阵挛发作模型小鼠大脑额叶皮层、下丘脑、纹状体和海马中兴奋性和抑制性氨基酸含量的影响。下丘脑的天冬氨酸和海马的谷氨酸等兴奋性氨基酸水平分别下降了 20.8% 和 16.7%，甘氨酸、GABA 和牛磺酸等抑制性氨基酸水平也在 MES 施用 5 分钟后平均下降了 16-20% ，这表明氨基酸神经传递已经耗竭。胃内注射 200 毫克/千克剂量的 NaV（具有抗癫痫作用）可阻止 MES 诱导的下丘脑 GABA 含量和 GABA/谷氨酸比率的下降。NaV 同样也能降低完整组小鼠和癫痫发作后小鼠下丘脑、纹状体和海马的天门冬氨酸含量。胃内注射 60 毫克/千克剂量的 GIZh-298 可防止 MES 引起的 GABA/谷氨酸比率以及下丘脑中 GABA、甘氨酸和牛磺酸水平的降低。

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来源期刊

Neurochemical Journal 医学-神经科学

自引率

20.00%

发文量

审稿时长

>12 weeks

期刊介绍： Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.