PMID- 30483749
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20211015
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Jan
TI  - Dexmedetomidine attenuates the toxicity of beta‑amyloid on neurons and astrocytes by 
      increasing BDNF production under the regulation of HDAC2 and HDAC5.
PG  - 533-540
LID - 10.3892/mmr.2018.9694 [doi]
AB  - Cytotoxicity of beta-Amyloid (Abeta) 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 Abeta 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 Abeta 
      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 Abeta 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 Abeta. Abeta 
      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 
      Abeta‑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 Abeta cytotoxicity. These results suggested that the protective 
      effect of Dex against Abeta is particularly relevant to BDNF. Thus, the present 
      study provides a foundation for the further study of Dex protection against Abeta in 
      animal models and pre‑clinical researches.
FAU - Wang, Yueling
AU  - Wang Y
AD  - Department of Anesthesiology, Xiangya Hospital, Central South University, 
      Changsha, Hunan 410008, P.R. China.
FAU - Jia, Aijun
AU  - Jia A
AD  - Department of Respiratory Medicine and Intensive Care Unit, The Affiliated 
      Hospital of Guilin Medical University, Guilin, Guangxi 541000, P.R. China.
FAU - Ma, Wenjuan
AU  - Ma W
AD  - Department of Anesthesiology, Xiangya Hospital, Central South University, 
      Changsha, Hunan 410008, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181126
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 3.5.1.98 (Hdac2 protein, rat)
RN  - EC 3.5.1.98 (Hdac5 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Alzheimer Disease/drug therapy/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/*drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Dexmedetomidine/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Histone Deacetylase 2/*metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Histone Deacetylases/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotection/drug effects
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - beta-amyloid
OT  - dexmedetomidine
OT  - brain-derived neurotrophic factor
OT  - histone deacetylase 2
OT  - histone deacetylase 5
EDAT- 2018/11/30 06:00
MHDA- 2019/05/29 06:00
CRDT- 2018/11/29 06:00
PHST- 2018/02/05 00:00 [received]
PHST- 2018/06/06 00:00 [accepted]
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/11/29 06:00 [entrez]
AID - 10.3892/mmr.2018.9694 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Jan;19(1):533-540. doi: 10.3892/mmr.2018.9694. Epub 2018 Nov 
      26.