Related Experiment Video
Updated: Jul 10, 2025
Author Spotlight: A Personalized Approach Towards Investigating Alzheimer's Disease Using an In Vitro Blood-Brain Barrier Model
Published on: October 20, 2023
An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB
Yuancheng Weng1, Ningting Chen2, Rui Zhang3
1Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Abstract:
Pericyte is an indispensable cellular constituent of blood-brain barrier (BBB) and its homeostasis heavily rely on PDGFB-PDGFRβ 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.
Insights
Microglia-derived PDGFB is crucial for adult blood-brain barrier (BBB) integrity. Loss of this signaling impairs BBB function and survival under injury, highlighting microglia
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Pericytes are vital for blood-brain barrier (BBB) homeostasis, relying on PDGFB-PDGFRβ signaling.
- The primary sources of PDGFB in the central nervous system (CNS) and microglia's role in BBB integrity are not fully understood.
Purpose of the Study:
- To identify the main cellular sources of PDGFB in the CNS.
- To investigate the role of PDGFB from different cell types in maintaining BBB integrity in both young and adult mice.
- To determine if microglia respond to BBB insults by altering PDGFB expression.
Main Methods:
- Transcriptomic data analysis
- In situ hybridization
- Genetic manipulation to induce acute loss of PDGFB in specific cell types (microglia, endothelial cells)
- Assessment of BBB integrity
- Survival studies following endotoxin challenge
Main Results:
- PDGFB production shifts from endothelial cells in newborns to microglia in adults.
- Loss of microglial PDGFB severely compromises BBB integrity and survival in adult mice under endotoxin challenge.
- Loss of endothelial PDGFB significantly impairs CNS vasculature in neonates but has minimal effect on adult BBB.
- Microglia upregulate PDGFB expression in response to various BBB insults.
Conclusions:
- Microglia-derived PDGFB is essential for maintaining BBB integrity in adult mice under both normal and injury conditions.
- Endothelial cells are the primary source of PDGFB for CNS vasculature development in neonates.
- Microglia play a critical role in adult BBB protection and repair through PDGFB signaling.
More Related Videos
08:04Derivation, Expansion, Cryopreservation and Characterization of Brain Microvascular Endothelial Cells from Human Induced Pluripotent Stem Cells
Published on: November 19, 2020
16:26Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport
Published on: June 28, 2014
