• Yutian Yu, Xuejiao Jiang, Xian Fang, Yu Wang, Pengfei Liu, Jing Ling, Lingling Yu, Min Jiang, and Chunzhi Tang.
• Acupuncture Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Ninth School of Clinical Medicine, Peking University, Beijing, China. Electronic address: yutianyu@bjsjth.cn.
• Neuromodulation. 2023 Apr 1; 26 (3): 589600589-600.

ObjectivesTransauricular vagal nerve stimulation (taVNS) at 40 Hz attenuates hippocampal amyloid load in 6-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, but it is unclear whether 40-Hz taVNS can improve cognition in these mice. Moreover, the underlying mechanisms are still unclear.Materials And Methods6-month-old C57BL/6 (wild type [WT]) and APP/PS1 mice were subjected to 40-Hz taVNS. Novel Object Recognition and the Morris Water Maze were used to evaluate cognition. Hippocampal amyloid-β (Aβ)1-40, Aβ1-42, pro-interleukin (IL)-1β, and pro-IL-18 were measured using enzyme-linked immunosorbent assays. Hippocampal Aβ42, purinergic 2X7 receptor (P2X7R), nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, IL-1β, and IL-18 expression were evaluated by western blotting. Histologic assessments including immunofluorescence, immunohistochemistry, Nissl staining, and Congo red staining were used to assess microglial phagocytosis, neuroprotective effects, and Aβ plaque load.Results40-Hz taVNS improved spatial memory and learning in 6-month-old APP/PS1 mice but did not affect recognition memory. There were no effects on the cognitive behaviors of 6-month-old WT mice. taVNS at 40 Hz modulated microglia; significantly decreased levels of Aβ1-40, Aβ1-42, pro-IL-1β, and pro-IL-18; inhibited Aβ42, P2X7R, NLRP3, Caspase-1, IL-1β, and IL-18 expression; reduced Aβ deposits; and had neuroprotective effects in the hippocampus of 6-month-old APP/PS1 mice. These changes were not observed in 6-month-old WT mice.ConclusionOur results show that 40-Hz taVNS inhibits the hippocampal P2X7R/NLRP3/Caspase-1 signaling and improves spatial learning and memory in 6-month-old APP/PS1 mice.Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.

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