Therapeutic efficacy of repetitive transcranial magnetic stimulation in an animal model of Alzheimer’s disease

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.

Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer's disease (Review)

“…Notably, a number of studies have indicated an increase in endogenous neurotrophic content (BDNF) in the affected brain regions after TMS therapy ( 2 , 74 ). BDNF is a neurotrophin involved in synaptic plasticity changes and improves learning, memory and cognitive functions via the BDNF-tropomyosin receptor kinase B (TrkB) signaling pathway ( 32 , 74 ). Therefore, BDNF serves a critical role in memory formation and synapsis.…”

“…Furthermore, the expression levels of BDNF are altered in neurodegenerative disorders, for example the BDNF levels are decreased in AD ( 80 ). A study by Choung et al ( 32 ) revealed an increase in BDNF expression, as well as neuronal nuclear protein (NeuN) and neuroepithelial stem cell protein (Nestin), after 20 Hz HF-rTMS compared with the non-rTMS group or sham group in the hippocampus and cerebral cortex regions. It was concluded that rTMS exerted neurogenic and neuroprotective effects and promoted neurogenesis ( Table I ) ( 32 ).…”

“…A study by Choung et al ( 32 ) revealed an increase in BDNF expression, as well as neuronal nuclear protein (NeuN) and neuroepithelial stem cell protein (Nestin), after 20 Hz HF-rTMS compared with the non-rTMS group or sham group in the hippocampus and cerebral cortex regions. It was concluded that rTMS exerted neurogenic and neuroprotective effects and promoted neurogenesis ( Table I ) ( 32 ). A similar increase in BDNF has also been observed after rTMS treatment in a number of other studies ( 36 , 81 ).…”

“…Furthermore, in healthy volunteers, dopamine tends to increase following deep TMS therapy ( 105 ). In a recent study by Choung et al ( 32 ), HF (20 Hz) and LF (1 Hz) rTMS were applied to assess dopamine levels and receptor concentrations after rTMS application. The findings suggested that HF-rTMS and LF-rTMS increased the dopamine levels in the hippocampus.…”

“…Among the NIBS techniques, transcranial magnetic stimulation (TMS) has emerged as a potential method providing a promising avenue to treat cognitive impairment, such as AD ( 2 , 29 ). A number of experimental studies on animal models and clinical trials have demonstrated the beneficial therapeutic effects of TMS on neurodegenerative disorders ( 30 , 31 ), including AD ( 32 , 33 ). Increasing evidence indicates that TMS treatment permits the neurophysiological (including motor cortex and neuronal activities) ( 34 , 35 ) and neurochemical (BDNF, TrkB) ( 36 , 37 ) functions to work more precisely, and TMS also regulates biomarkers level and further improves the accurate and precise functioning of neurons in AD ( Fig.…”