Dexmedetomidine attenuates the toxicity of β‑amyloid on neurons and astrocytes by increasing BDNF production under the regulation of HDAC2 and HDAC5

Wang,Yueling; Jia,Aijun; Ma,Wenjuan

doi:10.3892/mmr.2018.9694

Dexmedetomidine attenuates the toxicity of β‑amyloid on neurons and astrocytes by increasing BDNF production under the regulation of HDAC2 and HDAC5

Authors:
- Yueling Wang
- Aijun Jia
- Wenjuan Ma
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Affiliations: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Respiratory Medicine and Intensive Care Unit, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541000, P.R. China
Published online on: November 26, 2018 https://doi.org/10.3892/mmr.2018.9694
Pages: 533-540

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Abstract

Cytotoxicity of β-Amyloid (Aβ) is a major contributor to the pathogenesis of Alzheimer's disease. Dexmedetomidine (Dex) has been revealed to have multiple neuroprotective actions as a clinical anesthetic agent. The aim of the present study was to investigate the protection of Dex against Aβ in neurons and astrocytes, and the possible protective mechanisms. Primary neurons and astrocytes were isolated respectively from the hippocampus and cerebral cortex of neonatal Sprague Dawley rats. The neurons and astrocytes were incubated with Aβ in the presence or absence of Dex, which was followed by evaluation of the cell viability and apoptosis. Reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA assays were performed to assess the levels of specific genes or proteins. The results revealed that Aβ decreased the viabilities of neurons and astrocytes in a dose‑dependent manner, and elevated the rate of apoptosis. However, Dex attenuated the detrimental effects of Aβ. Aβ caused deacetylation of histone H3 by promoting the accumulation of histone deacetylase (HDAC)‑2 and HDAC5 in the cell nucleus, resulting in the reduced production of brain‑derived neurotrophic factor (BDNF). However, Dex reversed the Aβ‑induced deacetylation of histone H3 and thus, increased BDNF production. Using a HDAC inhibitor or recombinant BDNF protein also protected the neurons and astrocytes against Aβ cytotoxicity. These results suggested that the protective effect of Dex against Aβ is particularly relevant to BDNF. Thus, the present study provides a foundation for the further study of Dex protection against Aβ in animal models and pre‑clinical researches.

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