Early intervention attenuates synaptic plasticity impairment and neuroinflammation in 5xFAD mice.

Affiliation

Li K(1), Wang X(2), Jiang Y(1), Zhang X(1), Liu Z(2), Yin T(3), Yang Z(4).
Author information:
(1)College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China.
(2)Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Biomedical Engineering, Tianjin, 300192, China.
(3)Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Biomedical Engineering, Tianjin, 300192, China. Electronic address: [Email]
(4)College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China. Electronic address: [Email]

Abstract

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.