Boboc Ianis Kevyn Stefan, Dumitrelea Petrica-Daniel, Meca Andreea Daniela, Mititelu-Tartau Liliana, Bogdan Maria
Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Biomedicines. 2024 Nov 25;12(12):2689. doi: 10.3390/biomedicines12122689.
Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by progressive cognitive decline and behavioral disturbances, with an increasing incidence as the global population ages. This study investigates the effects of semaglutide (SEM), a glucagon-like peptide-1 analog, on cognitive function and anxiety-like behavior in a transgenic murine model of AD.
20 mice were randomly distributed into the following groups ( = 5): (WT + VEH) group: C57BL/6J + saline, (WT + SEM) group: C57BL/6J + semaglutide, (AD + VEH) group: AD + saline, (AD + SEM) group: AD + semaglutide. The animals underwent a four-week treatment, during which we monitored blood glucose levels, body weight, and responses in an open field test, novel object recognition test, social chamber test, and 0-maze test.
Post-treatment, SEM significantly reduced blood glucose levels in AD mice, aligning them with those of wild-type controls. Cognitive assessments indicated an improvement in the investigation index for SEM-treated mice compared to those receiving a vehicle, suggesting cognitive benefits. Although SEM did not significantly enhance motor and exploratory activities, it displayed a potential anxiolytic effect, particularly evident in the combined anxiety index, with notable differences observed before and after treatment in the AD group.
The findings of this pilot study suggest that SEM may play a dual role in managing AD by improving glycemic control and potentially enhancing cognitive function. As the landscape of AD treatment evolves, the comprehensive approach of utilizing SEM could pave the way for innovative interventions targeting the complex interplay of metabolic and cognitive dysfunctions in this challenging neurodegenerative disorder.
阿尔茨海默病（AD）是最常见的痴呆形式，其特征为进行性认知衰退和行为障碍，随着全球人口老龄化，发病率不断上升。本研究调查了胰高血糖素样肽-1类似物司美格鲁肽（SEM）对AD转基因小鼠模型认知功能和焦虑样行为的影响。
20只小鼠随机分为以下几组（每组n = 5）：（野生型+赋形剂）组：C57BL/6J + 生理盐水；（野生型+司美格鲁肽）组：C57BL/6J + 司美格鲁肽；（AD+赋形剂）组：AD + 生理盐水；（AD+司美格鲁肽）组：AD + 司美格鲁肽。动物接受为期四周的治疗，在此期间我们监测血糖水平、体重以及旷场试验、新物体识别试验、社交箱试验和零迷宫试验中的反应。
治疗后，司美格鲁肽显著降低了AD小鼠的血糖水平，使其与野生型对照小鼠的血糖水平一致。认知评估表明，与接受赋形剂的小鼠相比，接受司美格鲁肽治疗的小鼠的探究指数有所改善，提示有认知益处。虽然司美格鲁肽没有显著增强运动和探索活动，但它显示出潜在的抗焦虑作用，在综合焦虑指数中尤为明显，AD组治疗前后观察到显著差异。
这项初步研究的结果表明，司美格鲁肽可能通过改善血糖控制和潜在增强认知功能在AD管理中发挥双重作用。随着AD治疗格局的演变，利用司美格鲁肽的综合方法可能为针对这种具有挑战性的神经退行性疾病中代谢和认知功能障碍复杂相互作用的创新干预措施铺平道路。
