Objective: To investigate the effects of Dihuang Yinzi on cognitive function of APP/PS1 double transgenic mice and explore its underlying mechanisms.Methods: Forty - five male APP/PS1 double transgenic mice were randomly divided into 5 groups (9 mice per group) : namely the model group (normal saline), the donepezil hydrochloride group(0.84 mg/kg/d), and the low - dose, medium - dose, and high - dose Dihuang Yinzi groups (1.25, 2.5, and 5 g/kg/d, respectively). Additionally, 9 male C57BL/6J mice were used as the blank group (normal saline). All groups were treated continuously for 4 weeks. After 4 weeks, the Morris water maze test was used to evaluate spatial learning and memory abilities in each group. Nissl staining was performed to observe neuronal cells and Nissl bodies in the CA3 region of the hippocampus. Immunohistochemical (IHC) staining was used to observe NDRG2 and GFAP in the CA3 region of the hippocampus. Golgi staining was used to examine the morphology of dendritic spines in pyramidal neurons in the CA3 region of the hippocampus. Immunofluorescence staining was used to detect the expression of postsynaptic density protein - 95 (PSD95) and synaptophysin (SYN) in the CA3 region of the hippocampus. Western blot was used to measure the expression of NDRG2 and EAAT1 in the hippocampus.Results: Compared with the model group, the escape latency of the Morris water maze in each dose group of Dihuang Yinzi was reduced, and the residence time in the target quadrant and the number of crossings in the target quadrant were increased (P <0.01 or P < 0.05). The number of neurons, the number of dendritic branches, and dendritic spines were increased. PSD95 and SYN were up - regulated (P <0.05), while GFAP, NDGR2, and EAAT1 were decreased (P <0.01 or P <0.05).Conclusion: Dihuang Yinzi can improve the cognitive function of APP/PS1 double transgenic mice. Its mechanism of action may be related to down - regulating the expression of NDRG2, regulating astrocytes, subsequently down - regulating EAAT1, reducing the concentration of glutamate in the synaptic cleft, improving synaptic plasticity, and alleviating hippocampal neuronal damage.

Dihuang Yinzi  /  Astrocytes  /  N - myc downstream regulatory gene 2  /  Synaptic plasticity