Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Binbin Zhao; Dongfeng Wei; Qinghua Long; Qingjie Chen; Fushun Wang; Linlin Chen; Zefei Li; Tong Li; Tao Ma; Wei Liu; Linshuang Wang; Caishui Yang; Xiaxia Zhang; Ping Wang; Zhanjun Zhang

doi:10.1016/j.jpha.2023.10.006

Volume 14 Issue 3

Mar. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(3): 348-370

Binbin Zhao, Dongfeng Wei, Qinghua Long, Qingjie Chen, Fushun Wang, Linlin Chen, Zefei Li, Tong Li, Tao Ma, Wei Liu, Linshuang Wang, Caishui Yang, Xiaxia Zhang, Ping Wang, Zhanjun Zhang. Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 348-370. doi: 10.1016/j.jpha.2023.10.006

Citation:

Binbin Zhao, Dongfeng Wei, Qinghua Long, Qingjie Chen, Fushun Wang, Linlin Chen, Zefei Li, Tong Li, Tao Ma, Wei Liu, Linshuang Wang, Caishui Yang, Xiaxia Zhang, Ping Wang, Zhanjun Zhang. Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 348-370. doi: 10.1016/j.jpha.2023.10.006

Citation:

Binbin Zhao, Dongfeng Wei, Qinghua Long, Qingjie Chen, Fushun Wang, Linlin Chen, Zefei Li, Tong Li, Tao Ma, Wei Liu, Linshuang Wang, Caishui Yang, Xiaxia Zhang, Ping Wang, Zhanjun Zhang. Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 348-370. doi: 10.1016/j.jpha.2023.10.006

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Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

doi: 10.1016/j.jpha.2023.10.006

a. State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China;
b. Institute of Gerontology, Hubei University of Chinese Medicine, Wuhan, 430065, China;
c. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
d. Medical School, Hubei Minzu University, Enshi, Hubei, 445000, China;
e. HuBei University of Science and Technology, Xianning, Hubei, 437100, China;
f. Institute of Brain and Psychological Science, Sichuan Normal University, Chengdu, 610066, China;
g. Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, China;
h. Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China;
i. Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
j. School of Systems Science, Beijing Normal University, Beijing, 100875, China;
k. BABRI Centre, Beijing Normal University, Beijing, 100875, China

Funds:

This work was supported by National Natural Science Foundation of China (Grant No.: 82374317), State Key Program of National Natural Science of China (Grant Nos.: 82130119 and 82130118), Postdoctoral Research Foundation of China (Grant No.: 2021M690450), Traditional Chinese Medicine Research Project of Health Commission of Hubei Province (Grant No.: ZY2021M017), Hubei University of Chinese Medicine Funds for Distinguished Young Scholars (Grant No.: 2022ZZXJ004), National Natural Science Foundation of China (Grant No.: 82174210), and Fundamental Research Funds for the Central Public Welfare Research Institutes (Grant No.: ZZ14-FL-005).

Received Date: Jun. 14, 2023
Accepted Date: Oct. 19, 2023
Rev Recd Date: Sep. 25, 2023
Publish Date: Oct. 28, 2023

Abstract

Abstract

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ₄₂-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ₄₂-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.
- Alzheimer's disease,
- Synaptic currents,
- Mitophagy,
- Mitochondrial fusion and fission,
- Dengzhan Shengmai capsules

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References(75)

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