Transcranial Direct Current Stimulation Improves Cognitive Dysfunction in Amyloid Precursor Protein/Presenilin 1 Mice...

This study investigated the mechanisms by which transcranial direct current stimulation (tDCS) alleviated Alzheimer's disease (AD) progression.

Amyloid precursor protein (APP)/human presenilin 1 (PS1) transgenic mice (AD model) received tDCS (0.2 mA, anode electrode placed on the left frontal skull, 20 min/d for two weeks) and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) activator nigericin. Behavior tests evaluated spatial learning, recognition memory, and spontaneous exploration abilities in mice. Histopathologic changes in the hippocampal cornu ammonis area 1 (CA1) region and Aβ_1-42 deposition were observed using histologic staining and immunohistochemistry. Enzyme-linked immunosorbent assay was used to measure Aβ_1-40 and Aβ_1-42 expression. Classical microglia (M1)/alternative microglia (M2) polarization, inflammatory factors, and oxidative stress levels were assessed through immunofluorescence and kits. NLRP3 inflammasome indicators were detected by reverse transcription quantitative polymerase chain reaction and western blot.

After tDCS treatment, APP/PS1 mice exhibited shortened escape latency, increased platform crossings, and an elevated discrimination index. In the open field test, total movement distance and time spent in the center zone increased. The Aβ_1-42/40 ratio in the mouse hippocampal CA1 region decreased by 20.8%, whereas neurons and Nissl bodies increased, indicating that tDCS improved cognitive function. tDCS reduced M1 polarization, increased M2 polarization, and reduced neuroinflammation and oxidative stress in the hippocampal CA1 region of APP/PS1 mice. Moreover, tDCS suppressed microglial NLRP3/caspase-1 pathway activation and Aβ deposition in APP/PS1 mice. NLRP3/caspase-1 pathway activation partially reversed effects of tDCS on APP/PS1 mice.

This study highlights the potential therapeutic value of tDCS in AD mice. It reveals that tDCS promotes hippocampal microglial M2 polarization and Aβ degradation to curtail NLRP3/caspase-1 inflammasome pathway activation, thereby improving cognitive function in APP/PS1 mice.