Scholarlink

<p>This study was to investigate the effects of Toll-like receptor-3 (TLR3) activation on cognitive impairment and neuropathology in late-stage of Alzheimer’s disease in a mouse model. Amyloid protein precursor (APP)/presenilin-1 (PSEN1) (APP/PSEN1) mice were treated with Poly (I:C), a specific for TLR3. A panel of neurobehavioral tests were conducted to evaluate their cognitive functions. Aβ deposition, plasma Aβ levels, neuropathological changes, and activation of TLR3- TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling were assessed by magnetic resonance imaging (MRI), electrophysiological recordings, transmission electron microscopy, Western blotting, immunofluorescence staining, and qPCR. The data demonstrated that Poly (I:C) significantly attenuated cognitive and neuropathological impairments, compared with APP/PSEN1 mice without Poly (I:C) treatment. Administration of Poly (I:C) significantly reduced brain Aβ<sub>1-42</sub> deposition and the levels of Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub> in peripheral blood. In addition, treatment with Poly (I:C) significantly up-regulated the expression of anti-inflammatory factors and inhibited the expression of pro-inflammatory factors. The data indicated that systemic application of TLR3 agonist Poly(I:C) attenuated the brain damage, improved the cognitive function, and reduced the levels of Aβ<sub>1-42</sub> in brain and peripheral blood. The underlying mechanism might attribute to the up-regulation of p-IRF3 that increases the expression of anti-inflammatory factors and the inhibition of p-NF-κB that reduces the expression of pro-inflammatory factors.&#xa0;</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Late-Stage Activation of Toll-like receptor 3 Alleviates Cognitive Impairment and Neuropathology in an Alzheimer’s Disease Mouse Model

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月28日

查看全文
  • Taiyang Zhu,
  • Fanyu Shen,
  • Xiao Jia,
  • Hui Zhou,
  • Wanyan Ni,
  • Shang Wang,
  • Di Wu,
  • Huimin Gao,
  • Zhenying Shang,
  • Yan Zhou,
  • Jingjing Han,
  • Guoliang Jin,
  • Fuxing Dong,
  • Jie Zu,
  • Xinxin Yang,
  • Hongjuan Shi,
  • Chao Zhou,
  • Fang Hua

摘要

This study was to investigate the effects of Toll-like receptor-3 (TLR3) activation on cognitive impairment and neuropathology in late-stage of Alzheimer’s disease in a mouse model. Amyloid protein precursor (APP)/presenilin-1 (PSEN1) (APP/PSEN1) mice were treated with Poly (I:C), a specific for TLR3. A panel of neurobehavioral tests were conducted to evaluate their cognitive functions. Aβ deposition, plasma Aβ levels, neuropathological changes, and activation of TLR3- TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling were assessed by magnetic resonance imaging (MRI), electrophysiological recordings, transmission electron microscopy, Western blotting, immunofluorescence staining, and qPCR. The data demonstrated that Poly (I:C) significantly attenuated cognitive and neuropathological impairments, compared with APP/PSEN1 mice without Poly (I:C) treatment. Administration of Poly (I:C) significantly reduced brain Aβ1-42 deposition and the levels of Aβ1-40 and Aβ1-42 in peripheral blood. In addition, treatment with Poly (I:C) significantly up-regulated the expression of anti-inflammatory factors and inhibited the expression of pro-inflammatory factors. The data indicated that systemic application of TLR3 agonist Poly(I:C) attenuated the brain damage, improved the cognitive function, and reduced the levels of Aβ1-42 in brain and peripheral blood. The underlying mechanism might attribute to the up-regulation of p-IRF3 that increases the expression of anti-inflammatory factors and the inhibition of p-NF-κB that reduces the expression of pro-inflammatory factors.