PMID- 37701546
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230915
IS  - 2220-3206 (Print)
IS  - 2220-3206 (Electronic)
IS  - 2220-3206 (Linking)
VI  - 13
IP  - 8
DP  - 2023 Aug 19
TI  - Dexmedetomidine mediates the mechanism of action of ferroptosis in mice with 
      Alzheimer's disease by regulating the mTOR-TFR1 pathway.
PG  - 511-523
LID - 10.5498/wjp.v13.i8.511 [doi]
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative 
      disorder, and there are currently no effective drugs to delay progression of the 
      disease. Ferroptosis may play a vital part in AD, and is therefore receiving 
      increasing attention by researchers. AIM: To investigate the effects of 
      dexmedetomidine (Dex) on ferroptosis in AD mouse hippocampus. METHODS: 
      Hippocampal neurons (HNs) HT22 were induced by amyloid beta-protein (Abeta) and both in 
      vitro and in vivo AD mouse models were prepared via injections. The cell-counting 
      kit-8 assay and immunofluorescence technique were adopted to determine cell 
      proliferation activity and intracellular Fe(2+) levels, and the TBA method and 
      microplate method were employed for malondialdehyde and glutathione measurements, 
      respectively. Hippocampal tissue damage was determined using hematoxylin and 
      eosin and Nissl staining. Mouse learning and memory ability in each group was 
      assessed by the Morris water maze test, and the expression levels of mammalian 
      target of rapamycin (mTOR) signal molecules and ferroptosis-related proteins 
      transferrin receptor 1 (TFR1), SLC7A11 and glutathione peroxidase 4 were examined 
      by western blotting. RESULTS: Dex enhanced lipid peroxidation and iron influx in 
      mouse HNs in both in vitro and in vivo experiments, while inhibition of the mTOR 
      axis blocked this process. These findings demonstrate that Dex can inhibit 
      ferroptosis-induced damage in mouse HNs by activating mTOR-TFR1 signaling to 
      regulate ferroptosis-associated proteins, thus alleviating cognitive dysfunction 
      in AD mice. CONCLUSION: Dex can activate the mTOR-TFR1 axis to inhibit 
      ferroptosis in mouse HNs, thereby improving the learning and memory ability of 
      mice.
CI  - (c)The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Qiao, Li
AU  - Qiao L
AD  - Intensive Care Unit, Peking University International Hospital, Beijing 102206, 
      China.
FAU - Li, Gang
AU  - Li G
AD  - Intensive Care Unit, Peking University International Hospital, Beijing 102206, 
      China. ligang1@pkuih.edu.cn.
FAU - Yuan, Hong-Xun
AU  - Yuan HX
AD  - Intensive Care Unit, Peking University International Hospital, Beijing 102206, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230819
PL  - United States
TA  - World J Psychiatry
JT  - World journal of psychiatry
JID - 101610480
PMC - PMC10494775
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Dexmedetomidine
OT  - Ferroptosis
OT  - Mammalian target of rapamycin
OT  - Mice
COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of 
      interest for this article.
EDAT- 2023/09/13 06:42
MHDA- 2023/09/13 06:43
PMCR- 2023/08/19
CRDT- 2023/09/13 04:08
PHST- 2023/06/06 00:00 [received]
PHST- 2023/07/06 00:00 [revised]
PHST- 2023/07/27 00:00 [accepted]
PHST- 2023/09/13 06:43 [medline]
PHST- 2023/09/13 06:42 [pubmed]
PHST- 2023/09/13 04:08 [entrez]
PHST- 2023/08/19 00:00 [pmc-release]
AID - 10.5498/wjp.v13.i8.511 [doi]
PST - epublish
SO  - World J Psychiatry. 2023 Aug 19;13(8):511-523. doi: 10.5498/wjp.v13.i8.511. 
      eCollection 2023 Aug 19.