Impact of NMDA receptors block versus GABA-A receptors modulation on synaptic plasticity and brain electrical activity in metabolic syndrome

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences Pub Date : 2024-03-01 DOI:10.1016/j.advms.2024.03.008

Shaimaa Nasr Amin , Sherif Ahmed Shaltout , Walaa Bayoumie El Gazzar , Noha Samir Abdel Latif , Ghadah Nazar Al-jussani , Yasmeen Jamal Alabdallat , Khaled Anwer Albakri , Dalia Azmy Elberry

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Abstract

Purpose

Metabolic syndrome (MetS) is a common disorder associated with disturbed neurotransmitter homeostasis. Memantine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, was first used in Alzheimer's disease. Allopregnanolone (Allo), a potent positive allosteric modulator of the Gamma-Amino-Butyric Acid (GABA)-A receptors, decreases in neurodegenerative diseases. The study investigated the impact of Memantine versus Allo administration on the animal model of MetS to clarify whether the mechanism of abnormalities is related more to excitatory or inhibitory neurotransmitter dysfunction.

Materials and methods

Fifty-six male rats were allocated into 7 groups: 4 control groups, 1 MetS group, and 2 treated MetS groups. They underwent assessment of cognition-related behavior by open field and forced swimming tests, electroencephalogram (EEG) recording, serum markers confirming the establishment of MetS model and hippocampal Glial Fibrillary Acidic Protein (GFAP) and Brain-Derived Neurotrophic Factor (BDNF).

Results

Allo improved anxiety-like behavior and decreased grooming frequency compared to Memantine. Both drugs increased GFAP and BDNF expression, improving synaptic plasticity and cognition-related behaviors. The therapeutic effect of Allo was more beneficial regarding lipid profile and anxiety. We reported progressive slowing of EEG waves in the MetS group with Memantine and Allo treatment with increased relative theta and decreased relative delta rhythms.

Conclusions

Both Allo and Memantine boosted the outcome parameters in the animal model of MetS. Allo markedly improved the anxiety-like behavior in the form of significantly decreased grooming frequency compared to the Memantine-treated groups. Both drugs were associated with increased hippocampal GFAP and BDNF expression, indicating an improvement in synaptic plasticity and so, cognition-related behaviors.

Abstract Image

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阻断 NMDA 受体与调节 GABA-A 受体对代谢综合征患者突触可塑性和脑电活动的影响。

目的：代谢综合征（MetS）是一种与神经递质平衡紊乱有关的常见疾病。美金刚是一种 N-甲基-d-天冬氨酸受体（NMDAR）拮抗剂，最早用于治疗阿尔茨海默病。异丙肾上腺酮（Allo）是一种强效的γ-氨基丁酸（GABA）-A受体正异位调节剂，在神经退行性疾病中的作用下降。本研究调查了美金刚与 Allo 的施用对 MetS 动物模型的影响，以明确异常机制更多地与兴奋性还是抑制性神经递质功能障碍有关：将 56 只雄性大鼠分为 7 组：4 组为对照组，1 组为 MetS 组，2 组为 MetS 治疗组。它们接受了认知相关行为的评估，包括开阔地和强迫游泳测试、脑电图（EEG）记录、确认 MetS 模型建立的血清标记物以及海马胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）：与美金刚相比，Allo能改善焦虑样行为并降低梳理频率。两种药物都能增加 GFAP 和 BDNF 的表达，改善突触可塑性和认知相关行为。Allo 对血脂和焦虑的治疗效果更好。我们发现，在美金刚和阿洛的治疗下，MetS组的脑电图波逐渐减慢，相对θ节律增加，相对δ节律减少：结论：Allo 和 Memantine 都能提高 MetS 动物模型的结果参数。与美金刚治疗组相比，Allo明显改善了焦虑样行为，表现为梳理频率明显降低。这两种药物都与海马 GFAP 和 BDNF 表达的增加有关，表明突触可塑性得到了改善，从而改善了认知相关行为。

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来源期刊

Advances in medical sciences 医学-医学：研究与实验

CiteScore

5.00

自引率

0.00%

发文量

审稿时长

25 days

期刊介绍： Advances in Medical Sciences is an international, peer-reviewed journal that welcomes original research articles and reviews on current advances in life sciences, preclinical and clinical medicine, and related disciplines. The Journal’s primary aim is to make every effort to contribute to progress in medical sciences. The strive is to bridge laboratory and clinical settings with cutting edge research findings and new developments. Advances in Medical Sciences publishes articles which bring novel insights into diagnostic and molecular imaging, offering essential prior knowledge for diagnosis and treatment indispensable in all areas of medical sciences. It also publishes articles on pathological sciences giving foundation knowledge on the overall study of human diseases. Through its publications Advances in Medical Sciences also stresses the importance of pharmaceutical sciences as a rapidly and ever expanding area of research on drug design, development, action and evaluation contributing significantly to a variety of scientific disciplines. The journal welcomes submissions from the following disciplines: General and internal medicine, Cancer research, Genetics, Endocrinology, Gastroenterology, Cardiology and Cardiovascular Medicine, Immunology and Allergy, Pathology and Forensic Medicine, Cell and molecular Biology, Haematology, Biochemistry, Clinical and Experimental Pathology.