Background: Repetitive transcranial magnetic stimulation (rTMS) has been used to improve cognitive function, but the stimulation protocols are variable and the underlying mechanism is unclear. Therefore, we intend to examine whether 5Hz rTMS with 30% maximum output could improve cognitive functions in senescence-accelerated-prone mouse 8 (SAMP8) through changing synaptic plasticity. Methods: SAMP8 and senescence-accelerated-prone mouse/resistant 1 (SAMR1) (7-month old male) were randomly divided into 3 groups: SMAP8 rTMS group (P8-rTMS), SMAP8 sham-rTMS group (P8-sham), and SAMR1 sham-rTMS group (R1-sham). The P8-rTMS group was treated daily with 5Hz rTMS with 30% maximum output for 14 consecutive days, whereas the other two groups were controls without rTMS stimulation. Morris water maze (MWM) experiment was performed after rTMS or sham treatment to assess the effect of rTMS on cognitive function. Reverse transcription polymerase chain reaction and Western blot assays were used to detect the mRNA and protein expression of presynaptic Synapsin (SYN) and postsynaptic density 95 (PSD95) in the hippocampus of these mice. Results: The mean escape latency of the P8-rTMS group was significantly shorter than that of the P8-sham group. The number of platform crossings of the P8-rTMS group was significantly higher than that of the P8-sham group. rTMS significantly upregulated the protein and mRNA expression of SYN and PSD95 in the hippocampus of p8-rTMS mice compared to those of P8 sham mice. Conclusion: 5Hz rTMS with 30% maximum output enhances learning and memory in the SAMP8 mice. This improvement may be associated with the increased expression of synaptic structure proteins SYN and PSD95 in the hippocampus.

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