PMID- 34161158
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20220117
IS  - 1205-7541 (Electronic)
IS  - 0008-4212 (Linking)
VI  - 99
IP  - 9
DP  - 2021 Sep
TI  - Mild hyperhomocysteinemia induces blood-brain barrier dysfunction but not 
      neuroinflammation in the cerebral cortex and hippocampus of wild-type mice.
PG  - 847-856
LID - 10.1139/cjpp-2020-0507 [doi]
AB  - This study explored the potential effects of mild hyperhomocysteinemia (HHcy) on 
      the blood-brain barrier (BBB) and neuroinflammation. Seven-week-old male 
      wild-type C57BL/6 mice were fed normal mouse chow (the control group) or a 
      methionine-enriched diet (the HHcy group) for 14 weeks. Mice in the HHcy group 
      exhibited a slight increase in serum Hcy levels (13.56 +/- 0.61 mumol/L). Activation 
      of the ERK signaling pathway, up-regulation of matrix metalloproteinase-9 
      (MMP-9), and degradation of tight junction proteins (occludin and claudin-5) were 
      observed in both the cerebral cortex and hippocampus of mice with mild HHcy. 
      However, microglia were not activated and the levels of tumor necrosis factor-alpha 
      (TNF-alpha) and interleukin-1beta (IL-1beta) were not changed in either the cerebral cortex 
      or hippocampus of mice with mild HHcy. Moreover, the signaling activity of STAT3 
      also did not differ significantly between the two groups. These findings 
      demonstrate that the BBB is highly vulnerable to homocysteine insult. Even a 
      slight increase in serum homocysteine levels up-regulates MMP-9 expression and 
      disrupts the BBB integrity. Meanwhile, microglia activation or the STAT3 pathway 
      might not contribute to the effects of mild HHcy on the brain.
FAU - Chu, Min
AU  - Chu M
AD  - Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
FAU - Teng, Jijun
AU  - Teng J
AD  - Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
FAU - Guo, Lei
AU  - Guo L
AD  - Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
FAU - Wang, Yuyang
AU  - Wang Y
AD  - Department of Rehabilitation, the Affiliated Hospital of Qingdao University, 
      Qingdao 266000, Shandong, China.
FAU - Zhang, Liang
AU  - Zhang L
AD  - Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
FAU - Gao, Jing
AU  - Gao J
AD  - Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
FAU - Liu, Lijun
AU  - Liu L
AD  - Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 
      266000, Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20210623
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Cytokines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/*physiopathology
MH  - Cerebral Cortex/*immunology
MH  - Cytokines/analysis
MH  - Hippocampus/*immunology
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/*physiopathology
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Matrix Metalloproteinase 9/analysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroinflammatory Diseases/*etiology
MH  - STAT3 Transcription Factor/physiology
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - ERK
OT  - MMP-9
OT  - STAT3
OT  - barriere hematoencephalique
OT  - blood-brain barrier
OT  - homocysteine
OT  - homocysteine
OT  - microglia
OT  - microglie
OT  - neuro-inflammation
OT  - neuroinflammation
EDAT- 2021/06/24 06:00
MHDA- 2022/01/18 06:00
CRDT- 2021/06/23 17:14
PHST- 2021/06/24 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/06/23 17:14 [entrez]
AID - 10.1139/cjpp-2020-0507 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2021 Sep;99(9):847-856. doi: 10.1139/cjpp-2020-0507. 
      Epub 2021 Jun 23.