These results thus demonstrate that opioids prime neurons to undergo apoptosis by inducing TLR2 expression. Our data suggest that inhibition of TLR2 is capable of preventing opioids-induced damage to neurons. Opioids are powerful pain relievers, but also potent inducers of dependence and tolerance. Chronic morphine administration (via subcutaneous

pellet) induces morphine dependence in the nucleus accumbens, a key dependence region in the brain, yet the cellular mechanisms are mostly unknown. Toll-like receptor 2 (TLR2) plays an essential function in controlling innate and inflammatory responses. Using a knockout mouse lacking TLR2, we assessed the contribution of TLR2 to the development of morphine dependence and microglia activation. We report here that mice deficient in TLR2 inhibit morphine-induced Dinaciclib体外 the levels of microglia Saracatinib研究购买 activation and proinflammatory cytokines. Moreover, in TLR2 knockout mice the main symptoms of morphine withdrawal were significantly attenuated. Our data demonstrate that TLR2 is critical for opioid dependence and is a factor in response to innate immune response. As resveratrol derivatives, resveratrol

aliphatic acids were synthesized in our laboratory. Previously, we reported the improved pharmaceutical properties of the compounds compared to resveratrol, including better solubility in water and much tighter binding with human serum albumin. Here, we investigate the role of resveratrol aliphatic acids in Toll-like receptor 2 (TLR2)-mediated apoptosis. We showed that resveratrol aliphatic acid (R6A) significantly inhibits the expression of TLR2. In addition, overexpression of TLR2 in HEK293 cells caused a significant decrease in apoptosis after R6A treatment. Moreover, inhibition of TLR2

by R6A decreases serum deprivation-reduced the levels of phosphorylated Akt and phosphorylated glycogen synthase kinase 3(3 (GSK3β). Our study thus demonstrates that the resveratrol aliphatic acid inhibits cell apoptosis through TLR2 by the involvement of Akt/GSK3βpathway. TLR4 (Toll-like receptor-4), a key member of the TLRs family, has been well characterized by its function in induction of 不 inflammatory products of innate immunity. However, the involvement of TLR4 in a variety of apoptotic events with an unknown mechanism recently interests great research focus. Our investigation found that TLR4 promoted apoptotic signaling through affecting glycogen synthase kinase-3β(GSK-3(3) pathway in the serum deprivation (SD)-induced apoptotic paradigm. SD induces GSK-3βactivation in a pathway that leads to subsequent cell apoptosis. Intriguingly, this apoptotic cascade is amplified in presence of TLR4 whereas greatly attenuated byβ-arrestin 2, another critical molecule implicated in TLR4 mediated immune responses.