Histone deacetylase-6 modulates amyloid beta-induced cognitive dysfunction rats by regulating PTK2B.

Abstract

The aim of this study was to investigate the effects of histone deacetylase-6 (HDAC6) on the functional and pathological changes of the amyloid beta (Aβ)-induced cognitive dysfunction rats by regulating protein tyrosine kinase 2 beta (PTK2B). Ninety Sprague Dawley rats were randomly divided into nine groups, consisting of five experimental groups and four control groups. In five experimental groups, Aβ1-42 was infused intracerebroventricularly and 3 days later, rats in each group were infused intracerebroventricularly with tubastatin A hydrochloride (TSA), the HDAC6-specific inhibitor (Aβ + TSA group), theophylline, the HDACs agonist (Aβ + Theo group), PF431396 (PF), the PTK2B inhibitor (Aβ + PF group), the combination of PF and theophylline (Aβ + PF + Theo group), and normal saline (Aβ + normal saline group), respectively. Rats in four control groups took normal saline that was equivalent to the volume of Aβ1-42, and 3 days later, TSA (TSA group), theophylline (Theo group), (PF group, or normal saline group) was given at a volume of 5 µL for rats in each group. Our results showed that HDAC6 may not only lead to the deterioration of learning and memory abilities but also elevate the levels of Aβo and Tau phosphorylation in Aβ-induced cognitive dysfunction rats via upregulating PTK2B.

• Authors: Zhen Liu, Kai-Min Hao, Hao-Yu Wang, Wen-Xiu Qi
• Journal: Neuroreport (Neuroreport) Vol. 31 Issue 10 Pg. 754-761 (07 10 2020) ISSN: 1473-558X [Electronic] England
• PMID: 32453021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Focal Adhesion Kinase 2
• Ptk2b protein, rat
• HDAC6 protein, rat
• Histone Deacetylase 6

Topics

• Amyloid beta-Peptides (metabolism, toxicity)
• Animals
• Cognitive Dysfunction (chemically induced, metabolism)
• Focal Adhesion Kinase 2 (metabolism)
• Hippocampus (metabolism)
• Histone Deacetylase 6 (metabolism)
• Male
• Maze Learning (physiology)
• Rats, Sprague-Dawley