Diethyl butylmalonate attenuates cognitive deficits and depression in 5×FAD mice.

IF 3.2 3区医学 Q2 NEUROSCIENCES Frontiers in Neuroscience Pub Date : 2024-11-11 eCollection Date: 2024-01-01 DOI:10.3389/fnins.2024.1480000

Lai Yuan, Ge Song, Wangwei Xu, Shuni Liu, Yongsheng Zhang, Wei Pan, Xiaohui Ding, Linlin Fu, Qisi Lin, Fenfen Sun

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Abstract

Background: Alzheimer's disease (AD), characterized by cognitive impairment and depression, is currently one of the intractable problems due to the insufficiency of intervention strategies. Diethyl butylmalonate (DBM) has recently attracted extensive interest due to its anti-inflammatory role in macrophages. However, it is still unknown whether DBM has a beneficial effect on cognitive deficits and depression.

Methods: DBM was administrated to 5×FAD and C57BL/6J mice by intraperitoneal injection. Novel object recognition, Y-maze spatial memory, Morris water maze and nest building tests were used to evaluate cognitive function. Moreover, the tail suspension test, forced swimming test, open field test and the elevated plus maze test were used to assess depression. Transmission electron microscopy, Golgi-Cox staining, immunofluorescence, RT-qPCR and western blot were utilized to determine the neuropathological changes in the hippocampus and amygdala of mice.

Results: Multiple behavioral tests showed that DBM effectively mitigated cognitive deficit and depression in 5×FAD mice. Moreover, DBM significantly attenuated synaptic ultrastructure and neurite impairment in the hippocampus of 5×FAD mice, paralleled by the improvement of the deficits of PSD95 and BDNF proteins. In addition, DBM decreased the accumulation of microglia and downregulated neuroinflammation in the hippocampus and amygdala of 5×FAD mice.

Conclusion: This study provides evidence that DBM ameliorates cognitive deficits and depression via improvement of the impairment of synaptic ultrastructure and neuroinflammation, suggesting that DBM is a potential drug candidate for treating AD-related neurodegeneration.

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丁基丙二酸二乙酯可减轻 5×FAD 小鼠的认知缺陷和抑郁。

背景：阿尔茨海默病（AD）以认知障碍和抑郁为特征，由于干预策略不足，目前已成为难以解决的问题之一。丁基丙二酸二乙酯（DBM）因其在巨噬细胞中的抗炎作用最近引起了广泛关注。然而，DBM是否对认知障碍和抑郁症有益处仍是未知数：方法：给 5×FAD 和 C57BL/6J 小鼠腹腔注射 DBM。方法：给5×FAD和C57BL/6J小鼠腹腔注射DBM，采用新物体识别、Y迷宫空间记忆、莫里斯水迷宫和筑巢试验评估小鼠的认知功能。此外，还使用尾悬吊试验、强迫游泳试验、空地试验和高架加迷宫试验来评估抑郁。透射电子显微镜、Golgi-Cox 染色、免疫荧光、RT-qPCR 和 Western 印迹被用来确定小鼠海马和杏仁核的神经病理学变化：结果：多种行为测试表明，DBM能有效缓解5×FAD小鼠的认知缺陷和抑郁。此外，DBM能明显减轻5×FAD小鼠海马的突触超微结构和神经元损伤，同时改善PSD95和BDNF蛋白的缺陷。此外，DBM还减少了小胶质细胞的聚集，并下调了5×FAD小鼠海马和杏仁核的神经炎症：本研究提供了证据，证明 DBM 可通过改善突触超微结构和神经炎症的损伤来改善认知障碍和抑郁症，这表明 DBM 是治疗 AD 相关神经变性的潜在候选药物。

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来源期刊

Frontiers in Neuroscience NEUROSCIENCES-

CiteScore

6.20

自引率

4.70%

发文量

2070

审稿时长

14 weeks

期刊介绍： Neural Technology is devoted to the convergence between neurobiology and quantum-, nano- and micro-sciences. In our vision, this interdisciplinary approach should go beyond the technological development of sophisticated methods and should contribute in generating a genuine change in our discipline.