en Original Original <div style="text-align: justify;"><strong>Introduction</strong>: We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer Disease (AD) rat models. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death induced by A&beta;25-35 can be protected by thymol and carvacrol via Protein Kinase C (PKC) and Reactive Oxygen Species (ROS) pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in the AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKC&alpha; were examined in the hippocampal cells of the AD rat model.<br> <strong>Methods</strong>: To examine the thymol and carvacrol effects, we performed a behavioral test in AD rat models induced by A&beta;25&ndash;35 neurotoxicity. To access the underlying mechanism of the protective effects, western blotting was performed with antibodies against PKC&alpha;. We also measured the PKC activity assay by Elisa. Histopathological studies were carried out in the hippocampus with Hematoxylin and Eosin (H&E) staining.&nbsp;<br> <strong>Results</strong>: The escape latency increased in A&beta;-received rats compared to the control group, and thymol and carvacrol reversed this deficit. Furthermore, these compounds could enhance the PKC activity and increase the PKC&alpha; expression ratio. Moreover, H&E staining showed that A&beta; caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of A&beta; peptides.<br> Conclusion: This study suggests that Amyloid-Beta (A&beta;) results in memory decline and histochemical disturbances in the hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation.</div> Thymol, Carvacrol, Protein kinase C, Amyloid β, Alzheimer disease 295 304 http://bcn.iums.ac.ir/browse.php?a_code=A-10-666-2&slc_lang=en&sid=1 Zahra Azizi zahra121@yahoo.com 13700319475328460041403 13700319475328460041403 No Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Samira Choopani choopani_s@yahoo.com 13700319475328460041404 13700319475328460041404 No Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Mona Salimi salimimona@pasteur.ac.ir 13700319475328460041405 13700319475328460041405 No Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Nahid Majlessi mnahid@yahoo.com 13700319475328460041406 13700319475328460041406 No Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Nasser Naghdi naghdinasser@yahoo.com 13700319475328460041407 13700319475328460041407 Yes Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.