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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1480000
This article is part of the Research Topic Neuroinflammation and Neurodegenerative Diseases View all 12 articles

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

Provisionally accepted
Lai Yuan Lai Yuan 1,2Ge Song Ge Song 1,2Wangwei Xu Wangwei Xu 3,4Shuni Liu Shuni Liu 1,2Yongsheng Zhang Yongsheng Zhang 1,2Wei Pan Wei Pan 1*Linlin Fu Linlin Fu 1Qisi Lin Qisi Lin 3Sun Fenfen Sun Fenfen 1
  • 1 Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 2 First Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 3 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 4 Suqian Affiliated Hospital of Xuzhou Medical University, Suqian, China

The final, formatted version of the article will be published soon.

    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 (NOR), Y-maze spatial memory, Morris water maze and nest building test were used to evaluate cognitive function. Moreover, the tail suspension test, forced swimming test, open field test and the elevated plus maze 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.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.

    Keywords: Alzheimer's disease, cognitive, Depression, Neuroinflammation, synaptic plasticity, diethyl butylmalonate

    Received: 13 Aug 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Yuan, Song, Xu, Liu, Zhang, Pan, Fu, Lin and Fenfen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wei Pan, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China

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