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Diethyl butylmalonate attenuates cognitive deficits and depression in 5×FAD mice
Lai Yuan1,2, Ge Song1,2, Wangwei Xu3,4
1Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
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.
Insights
Diethyl butylmalonate (DBM) effectively treats Alzheimer's disease (AD) symptoms by improving cognitive deficits and depression. This compound ameliorates synaptic impairment and neuroinflammation, showing promise as a potential AD therapeutic.
Area of Science:
- Neuroscience
- Pharmacology
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) presents significant challenges due to cognitive impairment and depression.
- Current interventions for AD are insufficient, highlighting the need for novel therapeutic strategies.
- Diethyl butylmalonate (DBM) has demonstrated anti-inflammatory properties, but its efficacy in AD models is unexplored.
Purpose of the Study:
- To investigate the therapeutic potential of Diethyl butylmalonate (DBM) in an Alzheimer's disease (AD) mouse model.
- To evaluate DBM's effects on cognitive deficits and depression-like behaviors in 5×FAD mice.
- To elucidate the underlying mechanisms of DBM's action on synaptic plasticity and neuroinflammation in AD.
Main Methods:
- Administration of DBM via intraperitoneal injection to 5×FAD and control mice.
- Comprehensive behavioral assessments including novel object recognition, Y-maze, Morris water maze, nest building, tail suspension, forced swimming, open field, and elevated plus maze tests.
- Neurobiological analyses using transmission electron microscopy, Golgi-Cox staining, immunofluorescence, RT-qPCR, and western blot to examine hippocampal and amygdala pathology.
Main Results:
- DBM treatment significantly improved cognitive function and reduced depression-like behaviors in 5×FAD mice.
- DBM attenuated synaptic ultrastructural damage and neurite deficits, restoring PSD95 and BDNF protein levels in the hippocampus.
- DBM decreased microglial activation and downregulated neuroinflammation in the hippocampus and amygdala of 5×FAD mice.
Conclusions:
- DBM effectively ameliorates cognitive deficits and depression in a mouse model of Alzheimer's disease.
- The therapeutic effects of DBM are linked to the improvement of synaptic ultrastructure and the reduction of neuroinflammation.
- DBM represents a promising therapeutic candidate for treating Alzheimer's disease-related neurodegeneration.
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