Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Physiology, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Iran.
Life Sci. 2018 Jul 15;205:63-72. doi: 10.1016/j.lfs.2018.05.007. Epub 2018 May 4.
In recent years, inactivation of A adenosine receptors has been emerged as a novel strategy for treatment of several neurodegenerative diseases. Although numerous studies have shown the beneficial effects of A receptors blockade on spatial memory, the impacts of selective adenosine A receptors on memory performance has not yet been examined in the context of demyelination. In the present study, we evaluated the effect of A receptor antagonist SCH58261 on spatial memory and myelination in an experimental model of focal demyelination in rat fimbria. Demyelination was induced by local injection of lysolecithin (LPC) 1% (2 μl) into the hippocampus fimbria. SCH58261 (20 μg/0.5 μl or 40 μg/0.5 μl) was daily injected intracerebroventricularly (i.c.v.) for 10 days post LPC injection. The Morris water maze test was used to assess the spatial learning and memory on day 6 post lesion. Myelin staining and immunostaining against astrocytes/microglia were carried out 10 days post LPC injection. The administration of adenosine A receptor antagonist prevented the spatial memory impairment in LPC receiving animals. Myelin staining revealed that application of SCH58261 reduces the extent of demyelination areas in the fimbria. Furthermore, the level of astrocytes and microglia activation was attenuated following administration of A receptor antagonist. Collectively, the results of this study suggest that A receptor blockade can improve the spatial memory and protect myelin sheath, which might be considered as a novel therapeutic approach for multiple sclerosis disease.
近年来，腺嘌呤核苷受体失活已成为治疗多种神经退行性疾病的新策略。虽然许多研究表明 A 受体阻断对空间记忆有益，但在脱髓鞘背景下，选择性腺嘌呤 A 受体对记忆性能的影响尚未得到研究。在本研究中，我们评估了 A 受体拮抗剂 SCH58261 在大鼠穹窿边缘局灶性脱髓鞘模型中对空间记忆和髓鞘形成的影响。通过向海马穹窿内注射溶卵磷脂（LPC）1%（2 μl）诱导脱髓鞘。SCH58261（20 μg/0.5 μl 或 40 μg/0.5 μl）每天鞘内注射（i.c.v.），在 LPC 注射后 10 天。Morris 水迷宫试验用于评估损伤后第 6 天的空间学习和记忆。LPC 注射后 10 天进行髓鞘染色和针对星形胶质细胞/小胶质细胞的免疫染色。腺嘌呤 A 受体拮抗剂的给药可防止 LPC 接受动物的空间记忆障碍。髓鞘染色显示，SCH58261 的应用可减少穹窿边缘脱髓鞘区域的范围。此外，A 受体拮抗剂给药后星形胶质细胞和小胶质细胞激活水平减弱。总之，这项研究的结果表明，A 受体阻断可改善空间记忆并保护髓鞘，这可能被认为是多发性硬化症的一种新的治疗方法。
