PMID- 30618628
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 12
DP  - 2018
TI  - TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and 
      Mitochondrial Apoptotic Pathways After Experimental Stroke.
PG  - 475
LID - 10.3389/fncel.2018.00475 [doi]
LID - 475
AB  - Neurogenin-2 (Ngn2) is a basic helix-loop-helix (bHLH) transcription factor that 
      contributes to the identification and specification of neuronal fate during 
      neurogenesis. In our previous study, we found that Ngn2 plays an important role 
      in alleviating neuronal apoptosis, which may be viewed as an attractive candidate 
      target for the treatment of cerebral ischemia. However, novel strategies require 
      an understanding of the function and mechanism of Ngn2 in mature hippocampal 
      neurons after global cerebral ischemic injury. Here, we found that the expression 
      of Ngn2 decreased in the hippocampus after global cerebral ischemic injury in 
      mice and in primary hippocampal neurons after oxygen glucose deprivation (OGD) 
      injury. Then, transactivator of transcription (TAT)-Ngn2, which was constructed 
      by fusing a TAT domain to Ngn2, was effectively transported and incorporated into 
      hippocampal neurons after intraperitoneal (i.p.) injection and enhanced cognitive 
      functional recovery in the acute stage after reperfusion. Furthermore, TAT-Ngn2 
      alleviated hippocampal neuronal damage and apoptosis, and inhibited the 
      cytochrome C (CytC) leak from the mitochondria to the cytoplasm through 
      regulating the expression levels of brain-derived neurotrophic factor (BDNF), 
      phosphorylation tropomyosin-related kinase B (pTrkB), Bcl-2, Bax and cleaved 
      caspase-3 after reperfusion injury in vivo and in vitro. These findings suggest 
      that the downregulation of Ngn2 expression may have an important role in 
      triggering brain injury after ischemic stroke and that the neuroprotection of 
      TAT-Ngn2 against stroke might involve the modulation of BDNF-TrkB signaling that 
      regulates caspase-dependent and mitochondrial apoptotic pathways, which may be an 
      attractive therapeutic strategy for cerebral ischemic injury.
FAU - Zhao, Yu
AU  - Zhao Y
AD  - Department of Hygienic Toxicology, Public Health College, Harbin Medical 
      University, Harbin, China.
AD  - Department of Anesthesiology, Heilongjiang Provincial Hospital, Harbin, China.
FAU - Wang, Jinling
AU  - Wang J
AD  - Department of Emergency, Zhongshan Hospital, Xiamen University, Xiamen, China.
FAU - Du, Jiwei
AU  - Du J
AD  - Department of Nursing, Xiang'an Hospital, Xiamen University, Xiamen, China.
FAU - Li, Baixiang
AU  - Li B
AD  - Department of Hygienic Toxicology, Public Health College, Harbin Medical 
      University, Harbin, China.
FAU - Gou, Xingchun
AU  - Gou X
AD  - Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational 
      Medicine, Xi'an Medical University, Xi'an, China.
FAU - Liu, Jiannan
AU  - Liu J
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
FAU - Hou, Lichao
AU  - Hou L
AD  - Department of Anesthesiology, Xiang'an Hospital, Xiamen University, Xiamen, 
      China.
FAU - Sang, Hanfei
AU  - Sang H
AD  - Department of Anesthesiology, Xiang'an Hospital, Xiamen University, Xiamen, 
      China.
FAU - Deng, Bin
AU  - Deng B
AD  - Department of Anesthesiology, Xiang'an Hospital, Xiamen University, Xiamen, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20181214
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6302814
OTO - NOTNLM
OT  - apoptosis
OT  - brain-derived neurotrophic factor
OT  - global cerebral ischemia
OT  - neurogenin-2
OT  - transactivator of transcription domain
EDAT- 2019/01/09 06:00
MHDA- 2019/01/09 06:01
PMCR- 2018/01/01
CRDT- 2019/01/09 06:00
PHST- 2018/07/11 00:00 [received]
PHST- 2018/11/21 00:00 [accepted]
PHST- 2019/01/09 06:00 [entrez]
PHST- 2019/01/09 06:00 [pubmed]
PHST- 2019/01/09 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2018.00475 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2018 Dec 14;12:475. doi: 10.3389/fncel.2018.00475. 
      eCollection 2018.