Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Funcyion And Synaptic Plasticity In APP23/PS45 Mouse Model Of Alzheimer's Disease

Objective: The risk of dementia increases as the global aging population rapidly.Alzheimer's disease(AD)is a chronic neurodegenerative disease leading to dementia,which is characterized by progressive memory loss and other cognitive dysfunctions.Recent studies have attested that noninvasive repetitive transcranial magnetic stimulation(rTMS)may help improve cognitive function in patients with AD.However,the majority of these studies have paid attention to the effects of high-frequency rTMS on cognitive function,and little is known about low-frequency rTMS in AD treatment.In the present study,we wanted to determine whether low-frequency rTMS plays a role in the treatment of AD,and what mechanism leads to improvement on cognitive function of AD.Methods: Mice were randomly divided into four groups: WT,WT+rTMS,AD and AD+rTMS.1.Low-frequency rTMS treatment: AD+rTMS and WT+rTMS groups were treated with one session of low-frequency rTMS daily for 14 consecutive days.2.Behavioral tests: After daily treatment with low-frequency rTMS(1Hz)for 2 weeks,mice(aged 3 months)were subjected to water maze test.3.Electrophysiology in vitro: We used LTP to test the synaptic function in four groups.4.Immunohistochemistry staining: Mice were sacrificed after behavioral testing,the brain tissues were collected for immunohistochemistry staining to count the number of plaques.5.Western blotting: After behavioral testing,the brain tissues were gathered to detect the expression of APP?C99?C89 and BACE1.Results: The AD transgenic mice displayed a significant deficit in spatial learning,as reflected by taking much longer to find the hidden platform than WT control.Importantly,rTMS treatment shortened the escape latency for searching for the hidden platform in AD mice.In Electrophysiological recording,low-frequency rTMS treatment rescues impaired hippocampal LTP in AD mice.In both immunohistochemistry staining and Western blotting,low-frequency rTMS treatment reduces AD-related neuropathology in AD mice.Conclusion: Our study indicates that low-frequency rTMS can rescuethe deficits of cognitive and synaptic functions in APP23/PS45 double transgenic mice of AD,suggesting that low-frequency rTMS may serve as a highly effective anti-amyloid treatment in AD.