Cognitive impairment and hippocampal degeneration in aged rat models of type 2 diabetes with induced glycemic fluctuation: A pilot study

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-01-13 DOI:10.1016/j.brainres.2025.149452

Wei Yang , Si-Cong Si , Hong-Yu Luo, Yi-Xin Ma, Huan Zhao

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引用次数: 0

Abstract

Objective

Effective methods for establishing an aged animal model of diabetes and glycemic fluctuation have rarely been investigated. The aim of the study was to explore the feasibility of inducing glycemic fluctuation in aged Sprague–Dawley rats and to evaluate the corresponding changes in cognitive function.

Methods

Male rats aged 48 weeks were fed a high-fat and high-glucose diet and given streptozotocin intraperitoneally to establish a rat model of type 2 diabetes mellitus (T2DM). Then, glycemic fluctuation was induced via three different protocols: (1) intraperitoneal injection of glucose; (2) sequential fasting, insulin injection, and normal diet; and (3) intermittent intraperitoneal injections of glucose and insulin.

Results

All three protocols were effective at inducing glycemic fluctuation in aged rats with T2DM, with successful modeling rates of 60 %, 90 %, and 70 %, respectively. Aged T2DM rats with glycemic fluctuation showed significant increases in glycemic variability compared with controls, including in the mean blood glucose, postprandial glycemic excursion, largest amplitude of glycemic excursion, and standard deviation of blood glucose values (all P < 0.05). Additionally, rats with glycemic fluctuation had more severe insulin resistance and dyslipidemia (P < 0.05). Morris water maze testing showed a trend of longer escape latency in the navigation test for rats in the glycemic fluctuation groups, suggesting impaired cognitive function. Pathological analysis showed degenerative changes in the CA1 hippocampal region of rats in the glycemic fluctuation groups. Finally, differential gene expression analysis revealed 1323 significantly altered genes in the GV group, with 691 upregulated and 632 downregulated. The dysregulated genes were predominantly associated with the axon guidance pathway and potassium channel regulation.

Conclusions

The proposed protocols were effective at establishing an aged T2DM rat model with glycemic fluctuation, and rats with glycemic fluctuation exhibited diminished cognitive function.

Abstract Image

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认知障碍和海马变性老年2型糖尿病模型诱导血糖波动：一项初步研究。

目的：建立老年糖尿病动物模型的有效方法及血糖波动的研究很少。本研究旨在探讨诱导老年Sprague-Dawley大鼠血糖波动的可行性，并评价相应的认知功能变化。方法：48周龄雄性大鼠饲喂高脂高糖饲料，腹腔注射链脲佐菌素，建立2型糖尿病大鼠模型。然后，通过三种不同的方案诱导血糖波动：(1)腹腔注射葡萄糖；(2)顺序禁食、注射胰岛素、正常饮食；(3)间歇腹腔注射葡萄糖和胰岛素。结果：三种方法均能有效诱导老年T2DM大鼠的血糖波动，建模成功率分别为60%、90%和70%。与对照组相比，血糖波动的老年T2DM大鼠的血糖变异性显著增加，包括平均血糖、餐后血糖偏移、血糖偏移最大振幅和血糖值的标准差（均P）。结论：所提出的方案在建立血糖波动的老年T2DM大鼠模型方面是有效的，血糖波动大鼠表现出认知功能下降。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.