ArticleFrontiers in aging neuroscience2026
40-Hz transauricular vagal nerve stimulation rescues cognition of 9-month-old APP/PS1 mice via inhibiting hippocampal P2X7 receptor signaling.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The lack of any viable therapy for Alzheimer's disease (AD) evoked the study and utilization of neuromodulation. 40-Hz transauricular vagal nerve stimulation (taVNS) preliminarily showed effectiveness in mice with partial cognitive impairment in our previous work, yet 3 major problems remained unresolved. (1) Can 40-Hz taVNS rescue the cognition of mice exhibiting total cognitive impairment? (2) Are the cognition-rescuing effects of taVNS specific to 40 Hz stimulation? (3) Via P2X7R signaling? Thus, 3 parts were divided to address the above issues in this work using 9-month-old wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice. Behavioral examinations for cognition; western blotting (WB), enzyme-linked immunosorbent assays (ELISA) for Aβ load; WB and ELISA for the P2X7R signaling pathway; Nissl staining for neuroprotective effects were employed. 3 findings can be derived. (1) 40-Hz taVNS rescues cognition of the APP/PS1 mice aged 9 months (but is not effective in WT mice of the same age). (2) The cognition-rescuing effects of taVNS in APP/PS1 mice are frequency-specific, which is 40 Hz in this work (neither 8-Hz taVNS nor 80-Hz taVNS works). (3) The hippocampal P2X7R signaling is a critical mediator of the observed effects (inhibiting P2X7R had similar effects to 40-Hz taVNS, which counteracted activating P2X7R). Therefore, 40-Hz taVNS shows potential as a viable therapy option for AD, with the P2X7R being a prominent target.
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