Abstract
Objectives
Transauricular 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 Methods
6-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.
Results
40-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.
Conclusion
Our 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.
Keywords
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Article info
Publication history
Published online: May 17, 2022
Accepted:
March 14,
2022
Received in revised form:
February 4,
2022
Received:
December 31,
2021
Footnotes
Source(s) of financial support: This work was supported by National Administration of Traditional Chinese Medicine (2019XZZX-JB004), Youth Project of Beijing Shijitan Hospital (2019-q04, 2021-q01), National Natural Science Foundation of China (81803872, 82104980, 82174500, 82174479), and Beijing Municipal Administration of Hospitals Incubating Program (PZ2022005).
Conflict of Interest: The authors reported no conflict of interest.
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