Rosi Susanna, McGann Kristin, Hauss-Wegrzyniak Beatrice, Wenk Gary L
Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, Tucson 85724, USA.
J Neurochem. 2003 Jul;86(1):220-7. doi: 10.1046/j.1471-4159.2003.01825.x.
Alzheimer's disease (AD) is associated with glial activation and increased levels of pro-inflammatory cytokines. Epidemiological results suggest that anti-inflammatory therapies can slow the onset of AD. Adenosine, acting at type-2 receptors, is an effective endogenous anti-inflammatory agent that can modulate inflammation both in the periphery and the brain. We investigated changes in the expression of adenosine type-2B (A2B) receptors and a related intracellular second messenger during chronic brain inflammation and following treatment with the non-steroidal anti-inflammatory drug flurbiprofen and its nitric oxide (NO)-donating derivative, HCT1026. Chronic infusion of lipopolysaccharide (LPS) into the 4th ventricle of young rats induced brain inflammation that was associated with microglial activation and reduced neuronal immunoreactivity for adenosine A2B receptors in the cortex. Daily administration of HCT1026, but not flurbiprofen, reduced microglial activation, prevented the down-regulation of A2B receptors and elevated tissue levels of cAMP. The results suggest that a therapy using an NO-releasing NSAID might significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the activation of adenosine A2B receptors.
阿尔茨海默病（AD）与胶质细胞激活及促炎细胞因子水平升高有关。流行病学结果表明，抗炎疗法可延缓AD的发病。作用于2型受体的腺苷是一种有效的内源性抗炎剂，可调节外周和大脑中的炎症。我们研究了慢性脑部炎症期间以及用非甾体抗炎药氟比洛芬及其一氧化氮（NO）供体衍生物HCT1026治疗后，腺苷2B（A2B）受体和相关细胞内第二信使的表达变化。向幼鼠第四脑室慢性注入脂多糖（LPS）可诱发脑部炎症，这与小胶质细胞激活以及皮质中腺苷A2B受体的神经元免疫反应性降低有关。每日给予HCT1026而非氟比洛芬，可减少小胶质细胞激活，防止A2B受体下调，并提高组织中cAMP水平。结果表明，使用释放NO的非甾体抗炎药进行治疗可能会显著减轻驱动与AD相关病理过程的进程，并且该过程可能涉及腺苷A2B受体的激活。
