High-Fructose Diet-Induced Neuronal Plasticity in Rats: Implications for Acetylcholinergic Pathology and Therapeutic Approaches

IF 0.5 4区 医学 Q4 NEUROSCIENCES
L. G. Avetisyan, K. V. Simonyan, M. H. Danielyan, L. M. Sukiasyan, V. A. Chavushyan, A. S. Isoyan
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Abstract

Galantamine, a centrally-acting acetylcholinesterase (AChE) inhibitor, is currently used as a first-line therapy for the symptomatic treatment of Alzheimer’s disease. Long-term consumption of sugar-rich beverages has been shown to be associated with the development of various clinical conditions, including metabolic syndrome, impaired cholinergic transmission, and cognitive decline. The aim of this study was to determine the effect of long-term fructose consumption on changes in short-term plasticity (STP) parameters of rat brain lateral entorhinal cortex (lEC) neurons during high-frequency stimulation (HFS) of the cholinergic nucleus basalis magnocellularis (NBM) and to evaluate the therapeutic potential of Galantamine in neurodegeneration induced by diabetes. Using the method of determining AChE activity in brain slices from intact rats exposed to Galantamine, we revealed that AChE activity showed a declining trend in the NBM and lEC. Our findings indicated that STP changes were observed in the fructose group and were associated with degenerative disorders. Specifically, there was a dramatic decrease in the proportion and intensity of excitatory responses during HFS as well as a significant increase in the mean frequency of background spike activity in neuronal populations with all response types. Galantamine resulted in a recovery tendency for the balance and intensity of excitatory and inhibitory responses. A characteristic feature of the therapeutic effect of Galantamine is an increase in the share and expression of responses in the neuronal population, exhibiting tetanic depression and post-tetanic potentiation to NBM stimulation. This clearly indicates that these neurons play a key role in homeostatic plasticity and integration into neuronal chains of cholinergic projections.

Abstract Image

高果糖饮食诱导的大鼠神经元可塑性:乙酰胆碱能病理学和治疗方法的意义
摘要金刚烷胺是一种中枢作用型乙酰胆碱酯酶(AChE)抑制剂,目前被用作阿尔茨海默病对症治疗的一线疗法。研究表明,长期饮用含糖量高的饮料与各种临床症状的发生有关,包括代谢综合征、胆碱能传递受损和认知能力下降。本研究旨在确定长期饮用果糖对大鼠大脑外侧内侧皮层(lEC)神经元在胆碱能基底核(NBM)高频刺激(HFS)时的短期可塑性(STP)参数变化的影响,并评估加兰他敏对糖尿病诱发的神经退行性变的治疗潜力。通过测定暴露于加兰他敏的完整大鼠脑片的乙酰胆碱酯酶活性,我们发现乙酰胆碱酯酶活性在NBM和lEC呈下降趋势。我们的研究结果表明,果糖组大鼠的 STP 发生了变化,并且与退行性病变有关。具体来说,HFS期间兴奋性反应的比例和强度急剧下降,所有反应类型的神经元群中背景尖峰活动的平均频率显著增加。加兰他敏使兴奋性和抑制性反应的平衡和强度呈恢复趋势。加兰他敏治疗效果的一个特点是增加了神经元群中反应的份额和表达,表现出对 NBM 刺激的张力抑制和张力抑制后电位增强。这清楚地表明,这些神经元在胆碱能投射的同态可塑性和神经元链整合中发挥着关键作用。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
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.
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