Effects Of Music Intervention On Spatial Cognitive Ability Of APP/PS1 Mice And Its Mechanism

Alzheimers Disease(AD)is a kind of neurodegenerative Disease,which is mainly manifested by progressive cognitive dysfunction and neuropsychiatric symptoms.At present,there are more than 40 million AD patients in the world,and there are more than10 million AD patients in China.By 2050,there will be more than 115 million AD patients worldwide.Given the increasing prevalence and the limitations of drug action,it is important to search for non-drug interventions.Music therapy has been widely used in the treatment of clinical neuropsychiatric diseases,including AD,and studies have found that listening to music has a potential effect on slowing down the cognitive decline of AD.But until now,the exact mechanism by which music interferes has not been understood.In our previous work,we found that Mozart music and its rhythm can improve cognitive function.In this study,we focused on the effects of music on cognitive function in AD mice and explored its possible biological mechanisms.We randomly divided 3-month-old APP/PS1 AD mice into a Mozart group(listening to Mozart music)rhythm group(listening to Mozart music)blank group(no music intervention),and C57 mice were used as normal control.The spatial cognitive ability of mice at 3 months of age,6months of age,9 months of age and 12 months of age were detected,and the neuropathological changes related to AD and the changes of brain neuroinflammation were observed under different conditions,so as to explore the possible mechanism of music intervention in AD.The main work of this paper is as follows:1.Water maze test was used to observe the change of spatial cognitive ability of mice after music intervention.The results showed that at the age of 12 months,the escape latency of mice in the water maze was significantly different between the rhythm group and the blank group.It is suggested that Mozart rhythm intervention can slow down the decline of cognitive function in AD mice to a certain extent.2.According to the main neuropathological features of AD,we detected the expression level of Aβ42 Tau protein and the number of hippocampal neurons in different stages of mice by immunofluorescence staining.The expression levels of Aβ40 and P-TAU 181 in serum were determined by Enzyme linked immunosorbent assay(ELISA).Compared with C57 mice,AD mice showed corresponding neuropathological changes with increasing age.Compared with the blank group,the music intervention decreased the expression of Aβ40 and P-TAU 181 proteins in the hippocampus and serum,and reduced the loss of neurons,and the Mozart rhythm group had more significant effect.3.To understand whether music intervention can improve the progression of AD by reducing the immune inflammatory response in the brain,we measured the serum levels of pro-inflammatory factor(IL-1,IL-6,TNF-α)and the number of microglial cells in the hippocampus of mice at different stages.The results showed that the content of pro-inflammatory factor(IL-1,IL-6,TNF-α)in AD mice increased with the increase of age,while the number of microglia cells decreased with the increase of age.It is suggested that music intervention can reduce the production of proinflammatory factors and slow down the loss of microglia cells in AD mice,and with the extension of intervention time,the effect becomes more obvious.4.Further,we observed the intestinal morphology of mice in each group.The results showed that no obvious pathological changes of intestinal tract were found in each group,and there was no significant difference in the development of small intestinal villi between C57 mice and AD mice in blank group.However,the intestinal development(VH CD and VH/CD values)of mice in the music intervention group increased,suggesting that music intervention may affect the development of intestinal villi.In conclusion,this study suggests that music intervention can alleviate spatial cognitive impairment in APP/PS1 mice to a certain extent.It can reduce the expression of Aβ and Tau protein and slow down the loss of neurons.Music intervention may play a role by reducing the production of pro-inflammatory factors,slowing down the loss of microglia cells and reducing the neuroinflammatory response.Music intervention may affect the development of intestinal villi,thus improving the intestinal environment.The results of this study can provide theoretical support for music intervention in AD,which has potential clinical value.