Abstract
Electroacupuncture (EA) has become popular for its adjustable strength and frequency and easy quantification in the clinic and has demonstrated therapeutic potential for Alzheimer’s disease (AD). However, the mechanism remains unknown. Abnormally activated c-Jun N-terminal kinase (JNK) has been closely related to the pathological process of AD. The aim of this study was to investigate the effect of EA on cognitive impairment and the role of the JNK signaling pathway in AD model amyloid precursor protein (APP)/presenilin 1 (PS1) mice. The memory and learning ability of each group was assessed using the Morris Water Maze (MWM). Immunofluorescence, immunohistochemistry and Western blot were performed to measure the expression of APP, JNK, phosphorylated (P-)JNK, mitogen-activated protein kinase 4 (MKK4), MKK7, c-Jun and caspase-3 in hippocampal tissue samples in APP/PS1 mice after EA intervention. Obvious cognitive deficits were observed in the AD model APP/PS1 mice in the MWM test and were associated with JNK signaling pathway activation and APP upregulation. Four weeks of EA significantly ameliorated the cognitive impairments and inhibited JNK signaling pathway activation and APP upregulation. Taken together, the findings demonstrated that EA can reverse cognitive deficits and substantially lower the burden of APP in AD model APP/PS1 mice, at least partially through inhibiting the JNK signaling pathway and regulating apoptosis signals. Therefore, EA may offer an effective alternative therapeutic approach for AD.
Highlights
Alzheimer’s disease (AD), the most common cause of dementia, is a slowly progressive neurodegenerative disease that leads to impairments in several brain functions, such as learning and memory (McKhann et al, 2011)
The classic amyloid hypothesis states that the deposition of amyloid β (Aβ) protein (Morris et al, 1996; Pike et al, 2007), which is generated by β-amyloid precursor protein (APP) cleavage, is the major event in AD pathology
EA treatment improved the learning and memory ability of AD model APP/presenilin 1 (PS1) mice, which is consistent with a previous study
Summary
Alzheimer’s disease (AD), the most common cause of dementia, is a slowly progressive neurodegenerative disease that leads to impairments in several brain functions, such as learning and memory (McKhann et al, 2011). The patient’s ability to live and socialize is severely impaired. The “World Alzheimer Report 2018” noted that is one new dementia patient every three. Electro-Acupuncture Improved APP/PS1 Mice’s Cognition seconds in the world and that by 2050, there will be 152 million dementia patients worldwide. The aggregation of Aβ initiates irreversible neurodegeneration, which leads to neuronal cell damage and even death (Emerit et al, 2004). Studies have shown that dying cells in the brains of AD patients, including neurons, are characterized by apoptosis (Bredesen et al, 2006)
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