Abstract
The complexity of pathological mechanisms in Alzheimer’s disease (AD) poses significant challenges to the development of corresponding drugs. Symptom-specific pharmacological interventions and alternative treatments provide promising treatment possibilities. Therefore, we considered a combination of selegiline (SEL) and electroacupuncture (EA). We used an animal model with AD to investigate the effect of a combination of these treatments on cognitive function. 5XFAD mice received a week of SEL treatment and 2 weeks of EA. Novel object recognition and Y-maze tests were subsequently performed to assess their cognitive functions. To determine the molecular action of the combination treatment, Western blots, Aβ1-42 enzyme-linked immunosorbent assays (ELISA), and micro-positron-emission tomography were also performed to assess pathological markers and processes. The results were assessed based on the difference between untreated transgenic, SEL-treated, and SEL- and EA-treated groups of mice. Mice in the combined treatment group demonstrated significantly better cognitive functions, and lesser neuroinflammation than the comparative groups. In addition, mice treated with a combination of SEL and EA did not demonstrate a direct modulation of insoluble Aβ but demonstrated greater glucose metabolism. Our findings demonstrated that SEL combined with EA treatment was associated with better cognitive functioning due to inhibition of neuroinflammation and increased glucose metabolism relative to the comparative groups in a mouse model with AD.
Highlights
Alzheimer’s disease (AD), which is characterized by age-related neurodegenerative processes that lead to loss of cognitive and memory functions, is associated with neurofibrillary tangles formed by hyperphosphorylated tau and β-amyloid (Aβ) deposition, and neuroinflammation of the cerebral cortex and hippocampus (Choi et al, 2018; Oyama et al, 1993)
To evaluate the effect of SEL combined with EA treatment on cognitive function, novel object recognition (NOR) and Y-maze tests were performed with 5XFAD mice
To evaluate the effect of SEL combined with EA treatment on neuroinflammation, we examined the expression level of microglia, astrocyte, and neuroinflammatory protein, COX2, in mice treated with selegiline combined with electroacupuncture
Summary
Alzheimer’s disease (AD), which is characterized by age-related neurodegenerative processes that lead to loss of cognitive and memory functions, is associated with neurofibrillary tangles formed by hyperphosphorylated tau and β-amyloid (Aβ) deposition, and neuroinflammation of the cerebral cortex and hippocampus (Choi et al, 2018; Oyama et al, 1993). The neuroinflammation and amyloid plaques observed in AD are found to be associated with activated astrocytes and microglial cells. The latter is associated with proinflammatory factors, and tumor necrosis factor-alpha or interleukin 6 cytokines in serum and brain tissue (Fillit et al, 1991; Strauss et al, 1992). Combined Treatment in 5XFAD Mice precursor protein (β-APP) (Barger and Harmon, 1997). Autophagic dysfunction causes memory impairment due to Aβ accumulation in 5XFAD mice (Álvarez-Arellano et al, 2018). The same study demonstrated inflammasome activation caused by Aβ plaque accumulation due to autophagy impairment and microglial phagocytic activity reduction. There has been some evidence regarding the involvement of APOE protein in neuroinflammation and glucose metabolism during AD pathogenesis (Jagust and Landau, 2012; Liu et al, 2013)
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