Abstract
Previous studies on repetitive transcranial magnetic stimulation (rTMS) suggested potential neurorestorative properties in Alzheimer's disease (AD). This study aimed to investigate therapeutic effects of rTMS on an AD mouse model at high and low frequencies. The subject mice were allocated into the AD model group (AD induced by intracerebroventricular amyloid beta 42 oligomer [Aβ42] injection) and the saline-injected control group. Each group was subdivided according to rTMS treatment: high frequency (20 Hz), low frequency (1 Hz), and not rTMS-treated. Behavioural assessments with Y-maze test and novel object recognition task were performed; the results indicated cognition recovery by both the frequencies of rTMS after treatment in the AD model (Ps < 0.01). Tendency of further effects by high frequency compared to low frequency rTMS was also shown in Y-maze test. Neurotransmitter assay showed increment in dopamine concentration and upregulation of dopamine-receptor 4 (DR4) by rTMS in AD mice with higher response by high frequency stimulation (Ps < 0.05). Only high-frequency rTMS induced an elevation of brain-derived neurotrophic factor (BDNF) levels and enhanced the expression of Nestin and NeuN in the brain tissue (Ps < 0.05). Under in vitro conditions, Aβ42 incubated mouse hippocampal cell showed an increase in dopamine levels and BDNF by application of high-frequency rTMS treatment. In conclusion, rTMS might have a potential therapeutic effect on AD, and it seems to be related with dopaminergic activation. High frequency of stimulation seems to induce higher efficacy than that induced by low frequency, with elevated expressions of DR4 gene and neurogenic proteins.