| Background: Inflammation plays an important role in the pathogenesis of Alzheimer’s disease（AD）. It is reported that myeloid cells2（Trem2） gene variants is associated with AD. However, the underlying mechanisms are still unclear. Studies indicates that Trem2 affect the autophagy of microglia. In addition, a reciprocal inhibition between Trem2 and toll-like receptor 4（TLR4） has been reported in peripheral inflammation. Therefore, our experiment was designed to investigate the interaction between Trem2 and TLR4 in AD and to confirm whether the activation of Trem2 contributes to the development of AD.Methods: The C57BL/6 mice with lateral ventricle injection of Aβ1-42and the murine microglia cell line N9 treated with Aβ1-42 were used as the AD model in vivo and in vitro, respectively. The age-matched C57BL/6mice and N9 microglia untreated with Aβ1-42 were the control groups.Interleukin 4（IL-4） was used to activate Trem2 in microglia. The expression of Trem2, TLR4, caspase recruitment domain-containing protein 9（CARD9） and microtubule-associated protein 1A/1B-light chain 3（LC3） II/I was analyzed by immunohistochemistry, western blot, and reverse transcription-polymerase chain reaction. Morphology of microgliawas detected by electron microscope. Morris water maze tests were performed to detect the memory and cognition function of mice.Results: Aβ1-42 treated C57BL/6 mice showed cognitive impairment via Morris test, which suggested modeling success. We found that Trem2 increased in the AD model. In parallel, after activated by IL-4, increased Trem2 inhibited the expression of CARD9 and TLR4. The expression of LC3 II/I was increased, indicating the enhanced autophagy of microglia. In addition, the impairment of memory and cognitive function of AD model mice was improved eventually.Conclusions: The activation of Trem2 can inhibit the pro-inflammatory reaction of TLR4 and induce the autophagy of microglia,which improves the pathogenesis of AD. Thus, Trem2 is a promising new therapeutic strategy for the treatment of AD. |
