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.