System Normalized Gamma Oscillations of Brain Structures: Pharmacological Analysis of Neurochemical and Metabolic Processes

N. Karkischenko, Y. Fokin, S. Kharitonov
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Abstract

A systematic study of γ-oscillations was carried out using rats with chronically implanted electrodes in the proreal gyrus, somatosensory cortex, dorsal hippocampus, and hypothalamus. Brain electrograms (BE) were recorded and investigated using an original software and hardware module. Linear diagrams were constructed using a QMS17 device in a frequency range of 60–250 Hz or greater. A mathematical analysis, normalization, and rationing of the series of γ-rhythms under the action of gamma-aminobutyric acid (GABA), acetylcholine (ACC), and insulin relative to similar background series were performed by double discrete-time Fourier transform and double angle arctangent function, which allowed us to extract relevant information from extremely small (1–2 μV) values of γ-oscillations. The accumulation of the substances under study was achieved by introducing the Aminalon (GABA), Galantamine (ACC), and liposomal Insulin pharmaceuticals. The plasma concentrations of the studied drugs were verified by HPLC and mathematical modeling. The normalized BE (NBE) reflected the intracentral mechanisms of action of the tested drugs, which were characterized by a stable picture in the resting state of the animals and under the action of Aminalon, Galantamine, and Insulin at the peak of their plasma concentrations (according to pharmacokinetic parameters). The γ-activity of the brain is maintained at the systemic level. Blockade of γ-oscillations in the frontal pole leads to their activation in the associated brain structures: the hypo-thalamus, reticular formation, caudate nucleus, etc. Under the influence of Aminalon, the total depressive effects were observed over the entire analyzed range in the posterior nucleus of the hypothalamus and proreal gyrus, as well as activating effects in the frequency range 60–75 Hz in the anterior suprasylvian gyrus. Under the action of Galantamine, partial depressive effects in the hippocampus and hypothalamus were observed at   frequencies of about 60–65, 95–105, and 150 Hz. Under the action of liposomal Insulin, partial activating effects were noted in the anterior suprasylvian gyrus and in the dorsal hippocampus in the frequency range of 60–85 Hz.
大脑结构的系统归一化伽马振荡:神经化学和代谢过程的药理学分析
通过在大鼠前回、躯体感觉皮层、海马背侧和下丘脑长期植入电极,对γ振荡进行了系统研究。脑电图(BE)是用一个独创的软件和硬件模块记录和研究的。使用 QMS17 设备在 60-250 Hz 或更高频率范围内构建线性图。通过双离散时间傅里叶变换和双角反正切函数,对γ-氨基丁酸(GABA)、乙酰胆碱(ACC)和胰岛素作用下的γ-节律序列进行了数学分析、归一化和配比,使我们能够从极小(1-2 μV)的γ-振荡值中提取相关信息。通过引入阿米那龙(GABA)、加兰他敏(ACC)和脂质体胰岛素药物,实现了所研究物质的蓄积。研究药物的血浆浓度通过高效液相色谱法和数学模型进行了验证。归一化BE(NBE)反映了受试药物的中枢内作用机制,其特点是在动物静息状态下,以及在阿米那隆、加兰他敏和胰岛素作用下,其血浆浓度达到峰值时(根据药代动力学参数),情况稳定。大脑中的γ活性维持在全身水平。阻断额极的γ-振荡会导致相关大脑结构的激活:丘脑下部、网状结构、尾状核等。在氨马隆的作用下,下丘脑后核和前回(proreal gyrus)在整个分析范围内都出现了全面的抑郁效应,前上回(anterior suprasylvian gyrus)在 60-75 Hz 频率范围内也出现了激活效应。在加兰他敏的作用下,海马和下丘脑在大约 60-65、95-105 和 150 赫兹的频率范围内出现了部分抑制作用。在脂质体胰岛素的作用下,海马前上回和海马背侧在 60-85 赫兹的频率范围内出现了部分激活效应。
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