Research reportInhibition of JNK phosphorylation reverses memory deficit induced by β-amyloid (1-42) associated with decrease of apoptotic factors

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.

Research highlights▶ SP600125 pretreatment of the rats protected them against impairment of spatial learning induced by Aβ infusion. ▶ SP600125 pretreatment fortified the treated rats against memory impairment. This may indicate the positive effect of JNK inhibitors on preventing memory defect. ▶ Pretreatment of the rats with SP600125 inhibited the significant alterations in the apoptotic factors including caspase-3, Bax and Bcl-2. Increase in Aβ-induced caspase-3 reduced significantly in the SP600125 pretreated rats, while the Bcl-2/Bax ratio increased significantly in the SP600125 pretreated group. ▶ Aβ injection increased COX-2 expression, while pretreatment of the rats with SP600125 inhibited its expression.