Histone Deacetylase Class IIb Inhibition Improves Amyloid-β-induced Learning and Memory Deficits in Male Rats

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- (A) 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 A injections in male Wistar rats.Tubacin (HDAC6 inhibitor) and bufexamac (HDAC6 and 10 inhibitors) were microinjected 30 minutes after A injection.The possible molecular changes in the hippocampus following A 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 A 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 A 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.