期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 99, 期 9, 页码 847-856出版社
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/cjpp-2020-0507
关键词
homocysteine; ERK; MMP-9; blood-brain barrier; microglia; neuroinflammation; STAT3
资金
- Affiliated Hospital of Qingdao University
This study revealed that mild hyperhomocysteinemia can lead to BBB damage, disrupting brain structure. Even a slight increase in homocysteine levels can destabilize the BBB, but microglia activation and the STAT3 signaling pathway may not play a significant role in this process.
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 mu mol/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-1 beta (IL-1 beta) 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.
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