OO246 - EARLY ACTIVATION OF TOLL-LIKE RECEPTOR-3 REDUCES ATTENUATES PATHOLOGICAL PROGRESSION AND IMPROVES NEUROBEHAVIORAL FUNCTIONS IN APP/PS1 MOUSE MODEL OF ALZHEIMER'S DISEASE (ID 1514)
Abstract
Aims
Toll-like receptor 3 (TLR3), as a natural immune receptor, plays an important role in the activation and regulation of immune/inflammatory response in nervous system, which is the main pathological features of Alzheimer's disease (AD). The present study is to investigate the role of TLR3 in the pathophysiological process and neurobehavioral dysfunction of AD.
Methods
In the experiment, agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild type (WT) control mice starting from the age of 4 months to 9 months. At the age of 14 months, behavioral tests were detected. After that, Western blots and immunohistochemistry (IHC) staining were used to evaluate the level of Amyloid β protein (Aβ), activation of inflammatory cells, and neuron loss. In addition, levels of inflammatory cytokines were measured using quantitative PCR (qPCR).
Results
The results demonstrated that early-activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, early-activation of TLR3 reduced Aβ protein deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in hippocampus.
Conclusions
The results indicated that early activation of TLR3 mediated signaling reduced the pathological progression and neurobehavioral dysfunction in mouse model AD
