1. 线粒体分裂抑制剂 1 对多发性硬化小鼠神经营养因子、再生抑制信号通路 分子的影响.
- Author
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张 伟, 刘子铭, 张年萍, 田思勰, 张思羽, 李艳花, and 马存根
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MYELIN proteins , *BRAIN-derived neurotrophic factor , *NEUROTROPHIN receptors , *NEUROTROPHINS , *MYELIN oligodendrocyte glycoprotein , *NUCLEAR proteins , *PEPTIDES - Abstract
BACKGROUND: Decreased expression of neurotrophic factors and increased expression of regenerating inhibitors are the main mechanisms of nerve injury. It has been proven that mitochondrial fission inhibitor-1 can decrease clinical score and relieve pathological injury in a mouse model of multiple sclerosis. However, its neuroprotective effects still need to be further explored. OBJECTIVE: To observe the state of neurons and axons in a mouse model of experimental autoimmune encephalomyelitis and to evaluate the neuroprotective effect of mitochondrial fission inhibitor-1. METHODS: A mouse model of experimental autoimmune encephalomyelitis was prepared in C57BL/6 mice by immunizing with myelin oligodendrocyte glycoprotein peptide fragment 35-55. Animal models were randomly divided into two groups (n=15 per group): model group and mitochondrial fission inhibitor-1 group. Mice were euthanized and lumbar spinal cord consecutive sections were harvested at day 28 post immunization. Immunofluorescence staining was used to analyze the state of neuronal cell body and synapse, the phosphorylation level of dynamin-related protein 1, and the expression of neurotrophic factor, regeneration inhibitor and its signaling pathway molecules in spinal cord tissue. RESULTS AND CONCLUSION: Compared with the model group, treatment with mitochondrial fission inhibitor-1 increased the number of neurons marked by neuron-specific nuclear protein in the spinal cord tissue, improved neuronal body morphology, increased the length of synaptophysin-positive synapse, decreased the loss of Neurofilament M, and inhibited the phosphorylation of dynamin-related protein 1. Mitochondrial fission inhibitor-1 treatment could significantly promote the expression of glial cell-derived neurotrophic factor, ciliary neurotrophic factor, and brain-derived neurotrophic factor. Mitochondrial fission inhibitor-1 intervention could markedly reduce the expression of myelin-associated glycoprotein, axon growth inhibitory factor A, axon growth inhibitory factor protein receptor, p75 neurotrophin protein receptor, and Rho-related protein kinase II in the mouse model. To conclude, mitochondrial fission inhibitor-1 can inhibit the phosphorylation level of dynamin-related protein 1, increase the expression of neurotrophic factor protein, and reduce the expression of regeneration inhibitor and related signaling pathway molecular proteins, thus alleviating damage to spinal cord neuron cell bodies, axons, and cysts. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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