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Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome
- Source :
- Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-17 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Background It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. Main body Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. Conclusion Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 21
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.90537f0398824a53a236e43bd1d4910d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12974-024-03097-5