Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse

• Published in: Alzheimer's research & therapy 2023-02, Vol.15 (1), p.33-33, Article 33
• Main Authors: Wang, Shang, Zhu, Taiyang, Ni, Wanyan, Zhou, Chao, Zhou, Hui, Lin, Li, Hu, Yuting, Sun, Xiaoyu, Han, Jingjing, Zhou, Yan, Jin, Guoliang, Zu, Jie, Shi, Hongjuan, Yang, Xingxing, Zhang, Zuohui, Hua, Fang
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides; Amyloid beta-protein; Amyloid beta-Protein Precursor - genetics; Amyloid β protein; Analysis; Animals; Antibodies; Brain; Care and treatment; Cytokines; Development and progression; Disease Models, Animal; Hypotheses; Inflammation; Interferon; Kinases; Ligands; Mice; Mice, Transgenic; Nervous system; Neuroinflammation; Physiology, Pathological; Polymerase chain reaction; Presenilin-1 - genetics; Proteins; Signal transduction; Testing; TLR3; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-023-01186-w

Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid β-protein (Aβ), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aβ deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aβ clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.