Early intervention attenuates synaptic plasticity impairment and neuroinflammation in 5xFAD mice.
BACKGROUND
As an increasing population of Alzheimer's disease (AD) patients year by year, which is a serious threat to human health, an effective approach to prevent and treat AD is required. Biomarker changes relevant to β-amyloid (Aβ) 20 years or more in advance of cognitive impairment, so early intervention is a feasible idea for AD therapy. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive technique offers the possibility of early intervention.


OBJECTIVE
To explore the effect of high-frequency rTMS on the pathological symptoms of AD transgenic mice and its mechanisms, a figure-of-eight coil was placed 2 mm above the head of mouse to apply 20 Hz high-intensity rTMS for 14 consecutive days.


METHODS
In vivo electrophysiological recording, behavioral test, Western blots assay and immunofluorescence were used to measure the pathological symptoms of AD.


RESULTS
Our data showed that early intervention effectively reduced Aβ levels and the activation of microglia on the one hand, and decreased levels of pro-inflammatory cytokines including IL-6 and TNF-α as well as regulated PI3K/Akt/NF-κB signaling pathway on the other hand, which created a favorable brain environment. Thus, it increased the expression of synapse-associated proteins and improved neuronal synaptic plasticity in brain of early-stage of 5xFAD transgenic mice.


CONCLUSIONS
This study is the first to suggest that early intervention of 20 Hz rTMS ameliorates neuroinflammation to improve synaptic plasticity of early-stage of 5xFAD mice through PI3K/Akt/NF-κB signaling pathway.
['Li|Kai|K|', 'Wang|Xin|X|', 'Jiang|Yu|Y|', 'Zhang|Xiaochen|X|', 'Liu|Zhipeng|Z|', 'Yin|Tao|T|', 'Yang|Zhuo|Z|']
D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D000818:Animals D004195:Disease Models, Animal D006801:Humans D051379:Mice D008822:Mice, Transgenic D009473:Neuronal Plasticity D019869:Phosphatidylinositol 3-Kinases
Early intervention Synaptic plasticity Neuroinflammation 5xFAD mice Inflammatory cytokines Repeated transcranial magnetic stimulation