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Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Depletion of microglia mitigates cerebrovascular dysfunction in diet-induced obesity mice
1Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College, Wuhan, Hubei, China.
Abstract:
Obesity is frequently associated with cerebrovascular dysfunction; however, the underlying mechanism remains less well understood. In this study, by using pharmacological approaches, we show that neuroinflammation involving microglia plays an important role in obesity-related cerebrovascular dysfunction. PLX3397 treatment, which leads to depletion of microglia, reduced the wall thickness and collagen deposition in the basilar artery of diet-induced obesity (DIO) mice. Besides, the phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 was enhanced, suggesting improved endothelial function of the basilar artery. The wire myography data show that acetylcholine-elicited relaxation of basilar artery isolated from DIO mice was improved after the treatment with PLX3397. Moreover, our data demonstrate that brain administration of IL-18 impaired cerebrovascular function in mice with normal body weight. Together, these data suggest that neuroinflammation involving microglia is important in obesity-related vascular dysfunction in the brain.NEW & NOTEWORTHY We reported that microglia, the resident immune cells in the brain, contribute to obesity-related cerebrovascular dysfunction in mice. Moreover, we showed that excessive IL-18 can lead to vascular dysfunction in mouse brain.
Insights
Microglia-driven neuroinflammation contributes to obesity-related cerebrovascular dysfunction. Targeting microglia with PLX3397 improved basilar artery function in diet-induced obesity (DIO) mice.
Area of Science:
- Neuroscience
- Vascular Biology
- Immunology
Background:
- Obesity is linked to cerebrovascular dysfunction, but mechanisms are unclear.
- Neuroinflammation is a potential contributor to these vascular issues.
Purpose of the Study:
- To investigate the role of microglia-mediated neuroinflammation in obesity-related cerebrovascular dysfunction.
- To assess the therapeutic potential of targeting microglia.
Main Methods:
- Pharmacological depletion of microglia using PLX3397 in diet-induced obesity (DIO) mice.
- Assessment of basilar artery structure and function using histology and wire myography.
- Evaluation of endothelial nitric oxide synthase (eNOS) phosphorylation.
- Investigation of Interleukin-18 (IL-18) effects on cerebrovascular function.
Main Results:
- Microglia depletion reduced basilar artery wall thickness and collagen deposition in DIO mice.
- PLX3397 treatment enhanced eNOS phosphorylation and improved acetylcholine-induced relaxation in basilar arteries.
- Brain administration of IL-18 impaired cerebrovascular function in normal weight mice.
Conclusions:
- Neuroinflammation involving microglia is a key factor in obesity-related cerebrovascular dysfunction.
- Targeting microglia may offer a therapeutic strategy for obesity-associated brain vascular problems.
- Elevated IL-18 levels may contribute to vascular dysfunction in the brain.
