PMID- 29920330
OWN - NLM
STAT- MEDLINE
DCOM- 20190806
LR  - 20190806
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 73
DP  - 2018 Oct
TI  - DNA binding protein HMGB1 secreted by activated microglia promotes the apoptosis 
      of hippocampal neurons in diabetes complicated with OSA.
PG  - 482-492
LID - S0889-1591(18)30228-9 [pii]
LID - 10.1016/j.bbi.2018.06.012 [doi]
AB  - Type 2 diabetes mellitus (T2DM) complicated with obstructive sleep apnea (OSA) 
      may cause neuronal apoptosis and cognitive deficits, but the underlying 
      mechanisms remain unclear. We aimed to determine the relationship between the 
      activation of microglia and the apoptosis of hippocampal neurons, specifically in 
      terms of high mobility group box-1 (HMGB1), after high glucose (HG) and 
      intermittent hypoxia (IH) exposure. Diabetic KK-Ay mice and non-diabetic C57BL/6J 
      mice (C57 mice) underwent IH or normoxia (control) exposure for 4 weeks. 
      Cognitive function, microglial activation and hippocampal neuronal apoptosis were 
      assessed after IH or normoxia exposure. Compared with C57 control mice, KK-Ay 
      control mice exhibited increased cognitive dysfunction, microglial activation and 
      hippocampal neuronal apoptosis. There were no differences between untreated KK-Ay 
      control mice and C57 mice that had been exposed to IH. The abovementioned 
      responses were aggravated in IH-exposed KK-Ay mice compared with control KK-Ay 
      mice. In vitro, a cellular co-culture experiment showed that HG combined with IH 
      could activate BV2 microglia, leading to the release of neuroinflammatory factors 
      (ROS, TNF-alpha, IL-1beta) and mediating the apoptosis of HT22 cells via the 
      PI3K/Akt/GSK-3beta signaling pathway. Meanwhile, HMGB1 was actively secreted into 
      the extracellular environment from activated BV2 microglia. As a proinflammatory 
      factor, it was able to sustain microglial activation by directly acting on those 
      cells. The activation promoted positive feedback and aggravated neuronal damage 
      further. In a cellular monoculture or co-culture system, HMGB1 siRNA was able to 
      alleviate the activation of BV2 cells and the apoptosis of HT22 cells induced by 
      HG combined with IH. Our object is to show that inhibition of HMGB1 may break the 
      vicious cycle to prevent or treat neuroinflammation and hippocampal neuronal 
      apoptosis caused by T2DM complicated with OSA.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Shi, Yu
AU  - Shi Y
AD  - Respiratory Department, Tianjin Medical University General Hospital, Tianjin 
      Medical University, 300052 Tianjin, China.
FAU - Guo, Xiangyu
AU  - Guo X
AD  - Respiratory Department, Tianjin Medical University General Hospital, Tianjin 
      Medical University, 300052 Tianjin, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - The Second Hospital of Tianjin Medical University, 300211 Tianjin, China.
FAU - Zhou, Hanchi
AU  - Zhou H
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin 
      Metabolic Diseases Hospital & Institute of Endocrinology, Department of 
      Physiology, Tianjin Medical University, 300070 Tianjin, China.
FAU - Sun, Bei
AU  - Sun B
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin 
      Metabolic Diseases Hospital & Institute of Endocrinology, Department of 
      Physiology, Tianjin Medical University, 300070 Tianjin, China. Electronic 
      address: sun_peipei220@hotmail.com.
FAU - Feng, Jing
AU  - Feng J
AD  - Respiratory Department, Tianjin Medical University General Hospital, Tianjin 
      Medical University, 300052 Tianjin, China. Electronic address: zyyhxkfj@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180618
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (HMGB1 Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Diabetes Complications/metabolism
MH  - Diabetes Mellitus, Type 2/complications
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - HMGB1 Protein/metabolism/*physiology
MH  - Hippocampus/metabolism/physiology
MH  - Hypoxia/metabolism/*physiopathology
MH  - Inflammation/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/metabolism/physiology
MH  - Neurons/metabolism/physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction
MH  - Sleep Apnea, Obstructive/metabolism/physiopathology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Activated microglia
OT  - Cognitive deficits
OT  - HMGB1
OT  - Hippocampal neuronal apoptosis
OT  - Intermittent hypoxia
OT  - Type 2 diabetes mellitus
EDAT- 2018/06/20 06:00
MHDA- 2019/08/07 06:00
CRDT- 2018/06/20 06:00
PHST- 2017/12/02 00:00 [received]
PHST- 2018/06/11 00:00 [revised]
PHST- 2018/06/15 00:00 [accepted]
PHST- 2018/06/20 06:00 [pubmed]
PHST- 2019/08/07 06:00 [medline]
PHST- 2018/06/20 06:00 [entrez]
AID - S0889-1591(18)30228-9 [pii]
AID - 10.1016/j.bbi.2018.06.012 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2018 Oct;73:482-492. doi: 10.1016/j.bbi.2018.06.012. Epub 2018 
      Jun 18.