神经药理学报 ›› 2018, Vol. 8 ›› Issue (2): 28-28.
• 2018年全国老年痴呆与认知障碍相关疾病学术会议论文摘要—基础研究 • 上一篇 下一篇
YOU Ting-ting,CHENG Yu-fang,GUO Hai-biao,WANG Hai-tao,XU Jiang-ping
摘要: Background:Inhibition of phosphodiesterase 4 (PDE4) improves the learning and memory abilities in Alzheimer’s disease animal models. The cognition-enhancing effects of PDE4 inhibition involve reduced inflammatory responses in the brain. However,the underlying mechanisms are ill-understood. cAMP induces autophagy,and defi ciency of autophagy leads to elevated inflammatory factors. In the present study,we aimed to investigate the contribution of autophagy to the anti-inflammatory effect of PDE4 inhibitor ROF. Methods:Acidic vesicles were traced by Lysotracker( LYT) red and acridine orange( AO) staining. Autophagosomes in BV-2 cells were observed by immunofluorescence staining of microtubule-associated protein 1 light chain 3 (LC3). Aβ25-35 or lipopolysaccharide (LPS) with ATP were used to activate microglial cells and infl ammasome. Cytokine levels were measured by ELISA method. The levels of pro-infl ammatory factors and essential proteins involved in the formation of autophagosome were detected by Western blotting. Results:ROF increased the level of LC3-II,while the level of p62 was decreased. Enhanced fl uorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition,immunofl uorescence indicated a significant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion of pro-caspase-1 to cleaved-caspase-1 and increased the production of mature IL-1β. Interestingly,these effects were blocked by the treatment of ROF. Moreover,ROF decreased the apoptosis of neuronal N2a cells in conditioned media from BV-2 microglia. These effects were reversed by inhibition of microglial autophagy. Treatment with ROF also showed enhanced autophagy in mcie treated with LPS.Conclusions:PDE4 inhibitor ROF inhibits infl ammasome activities and reduces the release of IL-1β by inducing autophagy.