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<p>Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer’s disease (AD). Although acetylcholinesterase (AChE) inhibitors have been the mainstay of symptomatic treatment for over two decades, their limited efficacy and adverse effects underscore the need for alternative therapeutic approaches. Recent evidence indicates that mechanical stimulation can modulate neuronal and glial signaling through mechanotransduction, suggesting a potential strategy to enhance cognitive function via non-pharmacological means. Here, we developed a head-mounted vibrotactile stimulation system (HVSS) that delivers controlled vibration to the cranium and evaluated its effects in a pharmacological model of acute cholinergic dysfunction induced by scopolamine. To this end, male C57BL/6 mice received scopolamine (1&#xa0;mg/kg, i.p.; on days 7, 14, and 28) and were exposed to daily vibrotactile stimulation at 20, 40, or 80&#xa0;Hz for 28 days. Behavioral performance was assessed using passive avoidance and Morris water maze tests, followed by biochemical and histological analyses. HVSS at 40&#xa0;Hz and 80&#xa0;Hz significantly improved cognitive performance, enhanced hippocampal cholinergic function, reduced oxidative damage, and upregulated memory-related signaling genes, including <i>BDNF</i>, <i>PI3K</i>, <i>AKt</i>, <i>ERK1/2</i>, <i>CREB</i>, and <i>CAMK4</i>. These findings suggest that high-frequency HVSS improves memory hippocampal cholinergic function via activation of memory-related signaling pathways, highlighting its potential as a safe, non-pharmacological neuromodulatory strategy for cholinergic dysfunction-related cognitive decline.</p>

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Transcranial vibrotactile stimulation enhances hippocampal cholinergic signaling and memory through frequency-dependent mechanotransduction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月22日

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  • Ok-Hyeon Kim,
  • Chang-Ho Shin,
  • Min-Woo Cho,
  • Jae-Young Ha,
  • Jai Jun Choung,
  • Dong-Keun Song,
  • Jae-Yeong Choi,
  • Eun Seo Chang,
  • Hyun Jung Lee,
  • Sae-Kwang Ku

摘要

Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer’s disease (AD). Although acetylcholinesterase (AChE) inhibitors have been the mainstay of symptomatic treatment for over two decades, their limited efficacy and adverse effects underscore the need for alternative therapeutic approaches. Recent evidence indicates that mechanical stimulation can modulate neuronal and glial signaling through mechanotransduction, suggesting a potential strategy to enhance cognitive function via non-pharmacological means. Here, we developed a head-mounted vibrotactile stimulation system (HVSS) that delivers controlled vibration to the cranium and evaluated its effects in a pharmacological model of acute cholinergic dysfunction induced by scopolamine. To this end, male C57BL/6 mice received scopolamine (1 mg/kg, i.p.; on days 7, 14, and 28) and were exposed to daily vibrotactile stimulation at 20, 40, or 80 Hz for 28 days. Behavioral performance was assessed using passive avoidance and Morris water maze tests, followed by biochemical and histological analyses. HVSS at 40 Hz and 80 Hz significantly improved cognitive performance, enhanced hippocampal cholinergic function, reduced oxidative damage, and upregulated memory-related signaling genes, including BDNF, PI3K, AKt, ERK1/2, CREB, and CAMK4. These findings suggest that high-frequency HVSS improves memory hippocampal cholinergic function via activation of memory-related signaling pathways, highlighting its potential as a safe, non-pharmacological neuromodulatory strategy for cholinergic dysfunction-related cognitive decline.