en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Alzheimer&rsquo;s disease (AD) is a neurodegenerative disease associated with progressive impairment of cognitive function. The primary pathological features of AD include aggregation of amyloid-&beta; (A&beta;) and hyperphosphorylation of the tau protein. Histone deacetylases (HDACs) play a crucial role in the pathophysiology of neurodegenerative diseases. This study aimed to investigate the potential neuroprotective effects of HDAC6 and HDAC10 inhibition in a rodent model of AD.&nbsp;<br> <strong>Methods</strong>: Learning and memory deficits were induced by bilateral intra-hippocampal A&beta; injections in male Wistar rats. Tubacin (HDAC6 inhibitor) and bufexamac (HDAC6 and 10 inhibitors) were microinjected 30 minutes after A&beta; injection. The possible molecular changes in the hippocampus following A&beta; injection were also assessed by western blotting analysis of pCREB/CREB and Pp70/P70 ratios.&nbsp;<br> <strong>Results</strong>: Our results revealed that bufexamac significantly recovered learning and memory impairments induced by A&beta; in the Morris water maze&nbsp;(MWM) task. Tubacin improved memory decline without affecting learning. Bilateral intra-hippocampal injection of each of the HDAC inhibitors significantly increased the pCREB/CREB and Pp70/p70 ratios compared to the A&beta; group, which was concurrent with behavioral alterations.<br> <strong>Conclusion</strong>: HDAC IIb treatment may be a promising strategy for improving learning and memory impairments in an animal model of AD, suggesting that HDAC targeting is a valuable strategy for further investigation.</div> Alzheimer’s disease (AD), Bufexamac, Cyclic adenosine monophosphate response element binding protein (CREB), Histone deacetylase (HDAC) enzymes, Ribosomal protein S6 kinase, Tubacin 583 594 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2822-2&slc_lang=en&sid=1 Zahra Mansouri noorivahid@ymail.com 13700319475328460054291 13700319475328460054291 No Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Fereshteh Motamedi fmotamedi54@gmail.com 13700319475328460054292 13700319475328460054292 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Fariba Khodagholi khodagholi@sbmu.ac.ir 13700319475328460054293 13700319475328460054293 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Maryam Zahmatkesh zahmatkm@tums.ac.ir 13700319475328460054294 13700319475328460054294 Yes Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.