【Animal Modeling】-Effect of Shenzhiling Oral Liquid on Early Hippocampal Synapse and Myelin Changes in App/Ps1 Double Transgenic Mice

  Objective: To observe the early neuroprotective effect of Shenzhiling oral liquid on AD mice by observing the ultrastructure of myelin sheath and synapse in the CA1 region of the hippocampus and the special staining changes of myelin sheath in 3-month-old App/Ps1 double transgenic mice.

  METHODS: The App/Ps1 double transgenic mouse model formed by cross-breeding PrP-hAppk595N/M596L single-transgenic dementia model mice and PrP-hPs1dE9 single-transgenic dementia model mice is a common disease model for the study of Alzheimer's disease. 3-month-old App/Ps1 double-transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg·d)], high-dose Shenzhiling group [50 g/(kg·d)], and medium-dose Shenzhiling group [25g/(kg·d)], Shenzhiling low-dose group [12.5g/(kg·d)], 9 mice in each group; another 9 C57BL/6J mice of the same age and background were used as the control group. The mice were given intragastric administration for 3 months. After the experiment, the tissue in the CA1 region of the hippocampus of the mice was taken for electron microscopy to observe the myelin sheath and synapse-related ultrastructure in this region, and the myelin sheath was stained with fast blue staining of nerve myelin.

  RESULTS: Electron microscope observation showed that compared with the control group, the number of synapses in the CA1 region of the hippocampus decreased in the model group (P<0.01), the neuron structure showed degenerative changes, and the morphology of oligodendrocytes showed a pre-apoptotic state. Compared with the model group, the number of synapses in the hippocampal CA1 region of the mice in each drug intervention group increased (P<0.01), and the morphology and structure of neurons and oligodendrocytes were more complete and stained. Compared with the control group, the myelin fibers in the model group were significantly reduced and the staining became lighter, and the distribution of myelin fibers in each intervention group increased to varying degrees and the staining was deepened.

  Conclusion: Shenzhiling oral liquid may exert early neuroprotective effects on AD by increasing the number of synapses in the hippocampal CA1 region of App/Ps1 double-transgenic mice and improving the structure and morphology of myelin, oligodendrocytes and neurons.