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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

Alzheimer’s Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory ‘Wounding’ to Anti-inflammatory ‘Healing’

Author(s): Jiang He, Tao Liao, Guo-Xin Zhong, Ji-Da Zhang, Yan-Ping Chen, Qi Wang* and Qing-Ping Zeng*

Volume 14, Issue 10, 2017

Page: [1123 - 1135] Pages: 13

DOI: 10.2174/1567205014666170417111420

Price: $65

Abstract

Objective: The etiological initiators of neuroinflammation remain inconclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund’s adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer’s disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In contrast, electroacupuncture (EA) elevates TNF-α/IL-8 and declines IL-10/TH at first, but declines TNF-α/IL-8 and elevates IL-10/TH later. Upon impact on mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates but secondly attenuates CC-triggered signaling cascades leading to oxidation, nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises neurodegeneration by decreasing amyloid- β peptide (Aβ) and phosphorylated tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting biosynthetic enzyme choline acetyltransferase (ChAT).

Results: Conclusively, EA initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase brain pathogenesis via conversion from pro-inflammatory microglia to anti-inflammatory microglia.

Keywords: Alzheimer’s disease, electroacupuncture, inflammatory lesion, neuroinflammation, neurodegeneration, oxidative stress

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