Histone Deacetylase Class Iib Inhibition Improves Amyloid-Β-Induced Learning and Memory Deficits in Male Rats Publisher



Z Mansouri ZAHRA ; F Motamedi F ; F Khodagholi FARIBA ; M Zahmatkesh MARYAM
Source: Basic and Clinical Neuroscience Published:2025

Abstract

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease associated with progressive impairment of cognitive function. The primary pathological features of AD include aggregation of amyloid-β (Aβ) 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. Methods: Learning and memory deficits were induced by bilateral intra-hippocampal Aβ injections in male Wistar rats. Tubacin (HDAC6 inhibitor) and bufexamac (HDAC6 and 10 inhibitors) were microinjected 30 minutes after Aβ injection. The possible molecular changes in the hippocampus following Aβ injection were also assessed by western blotting analysis of pCREB/CREB and Pp70/P70 ratios. Results: Our results revealed that bufexamac significantly recovered learning and memory impairments induced by Aβ in the Morris water maze (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 Aβ group, which was concurrent with behavioral alterations. Conclusion: 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. © 2025 Elsevier B.V., All rights reserved.