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

[ Vol. 14 , Issue. 10 ]

Author(s):

Jiang He, Tao Liao, Guo-Xin Zhong, Ji-Da Zhang, Yan-Ping Chen, Qi Wang* and Qing-Ping Zeng*   Pages 1123 - 1135 ( 13 )

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

Affiliation:

Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, Clinical Medical College of Acupuncture, Guangzhou University of Chinese Medicine, Guangzhou, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, Clinical Pharmacology Institute, Guangzhou University of Chinese Medicine, Guangzhou, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou



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