چکیده:
Alzheimer’s disease (AD) is a kind of neurodegenerative disease that is associated with progressive impairment of cognitive function. The primary pathological features of AD include the aggregated amyloid-β (Aβ) and hyperphosphorylation of tau protein. Histone deacetylase enzymes (HDAC) contribute in pathophysiology of neurodegenerative diseases. This study has investigated the possible neuroprotective effects of HDAC6 and HDAC10 inhibition in a rodent-AD model.
Learning and memory deficits were induced by bilateral intra-hippocampal Aβ injection in the male Wistar rats. The Tubacin (HDAC6 inhibitor) and Bufexamac (HDAC6 and10 inhibitor) were microinjected 30 min following 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.
Our results revealed that Bufexamac significantly recovered learning and memory impairments induced by Aβ in the MWM task. Meanwhile, Tubacin improved memory decline without affecting learning. Bilateral intra-hippocampal injection of each of HDAC inhibitors significantly increased the pCREB/CREB and Pp70/p70 ratios compared to the Aβ group that were concurrent with behavioral alterations.
HDAC IIb treatment may be a promising strategy for improving the learning and memory impairments in an animal model of AD, suggesting that HDAC targeting is valuable strategy for further investigation.
Learning and memory deficits were induced by bilateral intra-hippocampal Aβ injection in the male Wistar rats. The Tubacin (HDAC6 inhibitor) and Bufexamac (HDAC6 and10 inhibitor) were microinjected 30 min following 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.
Our results revealed that Bufexamac significantly recovered learning and memory impairments induced by Aβ in the MWM task. Meanwhile, Tubacin improved memory decline without affecting learning. Bilateral intra-hippocampal injection of each of HDAC inhibitors significantly increased the pCREB/CREB and Pp70/p70 ratios compared to the Aβ group that were concurrent with behavioral alterations.
HDAC IIb treatment may be a promising strategy for improving the learning and memory impairments in an animal model of AD, suggesting that HDAC targeting is valuable strategy for further investigation.
نوع مطالعه: Original |
موضوع مقاله:
Cellular and molecular Neuroscience
دریافت: 1402/11/18 | پذیرش: 1403/5/28
دریافت: 1402/11/18 | پذیرش: 1403/5/28
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