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Publication : An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB.

First Author  Weng Y Year  2024
Journal  Brain Behav Immun Volume  115
Pages  705-717 PubMed ID  37992789
Mgi Jnum  J:343519 Mgi Id  MGI:7565057
Doi  10.1016/j.bbi.2023.11.023 Citation  Weng Y, et al. (2024) An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB. Brain Behav Immun 115:705-717
abstractText  Pericyte is an indispensable cellular constituent of blood-brain barrier (BBB) and its homeostasis heavily rely on PDGFB-PDGFRbeta signaling. However, the primary cellular sources of PDGFB in the central nervous system (CNS) are unclear. Microglia is not considered a component of BBB and its role in maintaining BBB integrity in steady state is controversial. In this study, by analyzing transcriptomic data and performing in situ hybridization, we revealed a transition of the primary central PDGFB producers from endothelial cells in newborns to microglia in adults. Acute loss of microglial PDGFB profoundly impaired BBB integrity in adult but not newborn mice, and thus, adult mice deficient of microglial PDGFB could not survive from a sublethal endotoxin challenge due to rampant microhemorrhages in the CNS. In contrast, acute abrogation of endothelial PDGFB had minimal effects on the BBB of adult mice but led to a severe impairment of CNS vasculature in the neonates. Moreover, we found that microglia would respond to a variety of BBB insults by upregulating PDGFB expression. These findings underscore the physiological importance of the microglia-derived PDGFB to the BBB integrity of adult mice both in steady state and under injury.
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