Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Behav Brain Res. 2011 Mar 1;217(2):424-31. doi: 10.1016/j.bbr.2010.11.017. Epub 2010 Nov 11.
Alzheimer's disease (AD) is the most common form of dementia that is degenerative and terminal disease. The main reason of the disease is still unknown. β-amyloid (Aβ) plaques are the important hallmarks of memory impairment in patients suffering from AD. Aggregation of these plaques in the hippocampus appears during the development of the disease. One of the prominent factors having crucial impact in this process is MAPK. JNK, as a member of MAPK family has a pivotal role, especially in cell survival. We hypothesized that JNK may have beneficial effect on the process of memory improvement. Hence, we performed Morris water maze to investigate the possible impact of JNK inhibitor on spatial memory in Aβ-injected rats. Our data indicated that intracerebroventricular administration of SP600125, a JNK inhibitor, could significantly decrease escape latency and increase time spent in target quadrant, in treatment group. Furthermore, we evaluated some of the apoptotic factors in the hippocampus of the treated rats. Based on our data, the inhibitor led to the significant decrease in the amount of caspase-3, TUNEL positive cells, cyclooxygenase-2 and increase in Bcl-2/Bax ratio. Given the possible neuroprotective effects of SP600125 on Aβ-induced memory impairment and apoptosis, our results may open a new avenue for the treatment of AD.
阿尔茨海默病（AD）是最常见的痴呆症形式，是一种进行性和终末期疾病。该病的主要原因仍不清楚。β-淀粉样蛋白（Aβ）斑块是 AD 患者记忆障碍的重要标志。这些斑块在疾病发展过程中在海马体中聚集。在这个过程中具有关键影响的突出因素之一是 MAPK。JNK 作为 MAPK 家族的一员，具有关键作用，尤其是在细胞存活方面。我们假设 JNK 可能对改善记忆过程有有益的影响。因此，我们进行了 Morris 水迷宫实验，以研究 JNK 抑制剂对 Aβ 注射大鼠空间记忆的可能影响。我们的数据表明，鞘内注射 JNK 抑制剂 SP600125 可显著降低逃避潜伏期并增加目标象限的停留时间。此外，我们评估了治疗组大鼠海马体中的一些凋亡因子。根据我们的数据，抑制剂导致 caspase-3、TUNEL 阳性细胞、环氧化酶-2 的含量显著减少，Bcl-2/Bax 比值增加。鉴于 SP600125 对 Aβ 诱导的记忆障碍和细胞凋亡可能具有神经保护作用，我们的结果可能为 AD 的治疗开辟新途径。
