ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1伪 levels in A尾-injected rats
- 作者：Ghorbangol Ashabi ; Mahmoudreza Ramin ; Pegah Azizi ; Zahra Taslimi ; Shabnam Zeighamy Alamdary ; Abbas Haghparast ; Niloufar Ansari ; Fereshteh Motamedi ; Fariba Khodagholi ; khodagholi@sbmu.ac.ir
- 关键词：A尾 ; amyloid beta ; AD ; Alzheimer's disease ; ANOVA ; Analysis of Variance ; APP ; amyloid precursor protein ; ARE ; antioxidant response element ; CREB ; Ca+/cAMP-response element binding protein ; ECL ; electrochemiluminescence ; ERK ; extracellular signal-regulated
- 刊名：Behavioural Brain Research
- 出版年：2012
- 期刊代码：3_01664328
- 类别：neu
- 出版时间：15 June, 2012
- 卷：232
- 期：1
- 页码：165-173
- 文件大小：1080 K
摘要
In this study, we investigated the effect of intracerebroventricular administration of ERK and p38 specific inhibitors, U0126 and PD169316, respectively, on learning and memory deficits induced by amyloid beta (A尾) in rats. To investigate the effects of these compounds on learning and memory, we performed Morris water maze (MWM) test. U0126 and/or PD169316 improved spatial learning in MWM in A尾-injected rats, 20 days after A尾-injection. To determine the mechanisms of action of U0126 and PD169316, we studies their effect on some intracellular signaling pathways such as Ca+/cAMP-response element binding protein (CREB), c-fos, and transcription factors that regulate mitochondrial biogenesis. Based on our data, CREB and c-fos levels decreased 7 days after A尾-injection, while U0126 and/or PD169316 pretreatments significantly increased these levels. Moreover, U0126 and PD169316 activated peroxisome proliferator-activated receptor gamma coactivator-1a, nuclear respiratory factor 1, and mitochondrial transcription factor A, 7 days after A尾-injection. Surprisingly, these factors were returned to vehicle level, 20 days after A尾-injection. Our findings reinforce the potential neuroprotective effect of these inhibitors against the A尾 toxicity.