Abstract:

Objective To analyze the effects of 40 Hz auditory stimulation on the learning and memory ability，amyloid precursor proteins，phosphorylated tau proteins，synapticproteins，inflammatory factors，and brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） pathway proteins in hippocampal tissue in sleep deprived mice，explore the mechanism of 40 Hz auditory stimulation to improve cognitive impairment induced by sleep deprivation. Methods Totally 18 C57BL/6j male mice were randomly divided into control group，the Alzheimer's disease（AD） model group，Alzheimer's disease model +40 Hz auditory stimulation （AD+40 Hz） group，six in each group. AD mouse model was constructed by intraperitoneal injection of D-galactose and gavage of AlCl₃. The AD+40 Hz group mice were stimulated with 40 Hz auditory stimulation for 14 days after model construction. The new object recognition（NOR） and Y maze were used to evaluate the cognitive function of mice in each group. The Western blotting was used to detect the protein expression levels of amyloid precursor protein（APP），p-Tau-S404，glial fibrillary acidic protein（GFAP），postsynaptic density protein 95（PSD95），synaptophysin（Syp），brain derived neurotrophic factor（BDNF） and tyrosine kinase receptor B（TrkB） in the prefrontal cortexand hippocampus. The quantitative real-time PCR（RT-qPCR） was used to detectthe expression levels of proinflammatory factors interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α） mRNA in the prefrontal cortex and hippocampus. Results Compared with the control group，the proportion of distance and duration of mice in the Y maze in the AD group was significantly reduced，and the differences were statistically significant（all P<0.05）. The expression levels of APP and p-Tau-S404 protein and the levels of IL-1β and TNF-α mRNA in theprefrontal cortex and hippocampus were significantly increased，and the differences were statistically significant（all P<0.05）.The expression level of GFAP protein in the prefrontal cortex and hippocampus were significantly decreased，and the differences were statistically significant（all P<0.05），the expression levels of PSD95，Syp，BDNF，and TrkB protein were significantly decreased（all P<0.05）.Compared with the AD group，the proportion of distance and duration of mice in the Y maze in AD+40 Hz group were increased significantly，and the differences were statistically significant（all P<0.05）. The expression levels of APP and p-Tau-S404 protein and the levels of IL-1β and TNF-α mRNA in the prefrontal cortex and hippocampus were significantly decreased，and the differences were statistically significant（all P<0.05）.The expression level of GFAP protein was significantly decreased（P<0.05），the expression levels of PSD95，Syp，BDNF，and TrkB protein were significantly increased，and the differences were statistically significant（all P<0.05）. Conclusion 40 Hz auditory stimulation can improve the pathological changes of β-amyloid protein and phosphorylated tau protein in AD mice，and improve synaptic plasticity in the prefrontal cortex and hippocampus by regulating the BDNF/TrkB signaling pathway，thereby improving cognitive impairment caused by AD.

Key words: Alzheimer's disease, 40 Hz auditory stimulation, Amyloid β-protein, Phosphorylated tau protein, BDNF/TrkB pathway