PMID- 31654225
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20211204
IS  - 1559-1174 (Electronic)
IS  - 1535-1084 (Print)
IS  - 1535-1084 (Linking)
VI  - 22
IP  - 2
DP  - 2020 Jun
TI  - Dexmedetomidine Protects Against Oxygen-Glucose Deprivation-Induced Injury 
      Through Inducing Astrocytes Autophagy via TSC2/mTOR Pathway.
PG  - 210-217
LID - 10.1007/s12017-019-08576-0 [doi]
AB  - Although there is an increment in stroke burden in the world, stroke therapeutic 
      strategies are still extremely limited to a minority of patients. We previously 
      demonstrated that dexmedetomidine (DEX) protects against focal cerebral ischemia 
      via inhibiting neurons autophagy. Nevertheless, the role of DEX in regulating 
      astrocytes autophagic status in oxygen-glucose deprivation, a condition that 
      mimics cerebral ischemia, is still unknown. In this study, we have shown that DEX 
      and DEX + RAPA (autophagy inducer) increased viability and reduced apoptosis of 
      primary astrocytes in oxygen-glucose deprivation (OGD) model compared with 
      DEX + 3-methyladenine (3-MA) (autophagy inhibitor). DEX induced the expression of 
      microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1, while reduced 
      the expression of p62 in primary cultured astrocytes through induction of 
      autophagy. In addition, DEX enhanced the expression of tuberous sclerosis complex 
      2 (TSC2) in primary cultured astrocytes, while reduced the expression of 
      mammalian target of rapamycin (mTOR). In conclusion, our study suggests that DEX 
      exerts a neuroprotection against OGD-induced astrocytes injury via activation of 
      astrocytes autophagy by regulating the TSC2/mTOR signaling pathway, which 
      provides a new insight into the mechanisms of DEX treatment for acute ischemic 
      injury.
FAU - Zhu, Chen
AU  - Zhu C
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 1838 
      Guangzhou Avenue N, Guangzhou, 510515, Guangdong, China.
FAU - Zhou, Quan
AU  - Zhou Q
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 1838 
      Guangzhou Avenue N, Guangzhou, 510515, Guangdong, China.
FAU - Luo, Cong
AU  - Luo C
AUID- ORCID: 0000-0002-4464-812X
AD  - Department of Anesthesiology, The Sixth People's Hospital of Chengdu, 16 Jianshe 
      Street S, Chengdu, 610051, Sichuan, China. mazuicong@163.com.
FAU - Chen, Ying
AU  - Chen Y
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 1838 
      Guangzhou Avenue N, Guangzhou, 510515, Guangdong, China. 604928687@qq.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191025
PL  - United States
TA  - Neuromolecular Med
JT  - Neuromolecular medicine
JID - 101135365
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 5142-23-4 (3-methyladenine)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - JAC85A2161 (Adenine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Astrocytes/*drug effects
MH  - Autophagy/*drug effects/physiology
MH  - Cell Hypoxia/*drug effects
MH  - Cells, Cultured
MH  - Dexmedetomidine/*pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Glucose/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/*physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Random Allocation
MH  - Reperfusion Injury/prevention & control
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - Tuberous Sclerosis Complex 2 Protein/physiology
PMC - PMC7230061
OTO - NOTNLM
OT  - Astrocytes
OT  - Autophagy
OT  - Dexmedetomidine
OT  - Ischemic stroke
OT  - Neuroprotection
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2019/10/28 06:00
MHDA- 2021/07/20 06:00
PMCR- 2019/10/25
CRDT- 2019/10/27 06:00
PHST- 2019/07/06 00:00 [received]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2019/10/27 06:00 [entrez]
PHST- 2019/10/25 00:00 [pmc-release]
AID - 10.1007/s12017-019-08576-0 [pii]
AID - 8576 [pii]
AID - 10.1007/s12017-019-08576-0 [doi]
PST - ppublish
SO  - Neuromolecular Med. 2020 Jun;22(2):210-217. doi: 10.1007/s12017-019-08576-0. Epub 
      2019 Oct 25.