Inhibition of HDAC6 expression decreases brain injury induced by APOE4 and Aβ co‑aggregation in rats

Ding,Yuexia; Kang,Airong; Tang,Qiling; Zhao,Ying

doi:10.3892/mmr.2019.10571

Inhibition of HDAC6 expression decreases brain injury induced by APOE4 and Aβ co‑aggregation in rats

Authors:
- Yuexia Ding
- Airong Kang
- Qiling Tang
- Ying Zhao
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Affiliations: Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China, Department of Respiration, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China
Published online on: August 8, 2019 https://doi.org/10.3892/mmr.2019.10571
Pages: 3363-3370

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Abstract

The present study aimed to explore the effects of histone deacetylase 6 (HDAC6) on brain injury in rats induced by apolipoprotein E4 (APOE4) and amyloid β protein alloform 1‑40 (Aβ1‑40) copolymerization. The rats were randomly divided into four groups: Control group, sham group, APOE4 + Aβ1‑40 co‑injection group (model group) and HDAC6 inhibitor group (HDAC6 group). The brain injury model was established by co‑injection of APOE4 + Aβ1‑40. Morris water maze experiment was used to observe the spatial memory and learning the ability of rats. Histological changes of the hippocampus were observed by hematoxylin and eosin staining. The mRNA expression levels of choline acetyltransferase (ChAT) and HDAC6 were detected by reverse transcription‑quantitative PCR. Immunohistochemistry was used to detect the protein expression of HDAC6. Western blotting was used to detect the protein expression levels of HDAC6, microtubule‑associated protein tau and glycogen synthase kinase 3β (GSK3β). APOE4 and Aβ1‑40 co‑aggregation decreased the short‑term spatial memory and learning ability of rats, whereas inhibition of HDAC6 activity attenuated the injury. Inhibition of HDAC6 activity resulted in an attenuation of the APOE4 and Aβ1‑40 co‑aggregation‑induced increase in the number of dysplastic hippocampal cells. Further experiments demonstrated that APOE4 and Aβ1‑40 co‑aggregation decreased the expression levels of ChAT mRNA, and the phosphorylation levels of tau GSK3β protein in the hippocampus, whereas inhibition of HDAC6 activity resulted in increased expression of ChAT mRNA, tau protein and GSK3β phosphorylation. The inhibition of HDAC6 activity was also demonstrated to reduce brain injury induced by APOE4 and Aβ1‑40 co‑aggregation in model rats.

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