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