ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1alpha levels in Abeta-injected rats.

Authors: Ashabi, G  Ramin, M  Azizi, P  Taslimi, Z  Alamdary, SZ  Haghparast, A  Ansari, N  Motamedi, F  Khodagholi, F 
Citation: Ashabi G, etal., Behav Brain Res. 2012 Jun 15;232(1):165-73. doi: 10.1016/j.bbr.2012.04.006. Epub 2012 Apr 9.
Pubmed: (View Article at PubMed) PMID:22510382
DOI: Full-text: DOI:10.1016/j.bbr.2012.04.006

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 (Abeta) 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 Abeta-injected rats, 20 days after Abeta-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 Abeta-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 Abeta-injection. Surprisingly, these factors were returned to vehicle level, 20 days after Abeta-injection. Our findings reinforce the potential neuroprotective effect of these inhibitors against the Abeta toxicity.


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CRRD Object Information
CRRD ID: 7242180
Created: 2013-03-29
Species: All species
Last Modified: 2013-03-29
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.