Department of Neurobiology; Graduate School of Biomedical Sciences; Schafer Lab; Department of Microbiology and Physiological Systems
Neuroscience and Neurobiology
Microglia, the resident macrophages of the central nervous system (CNS), are dynamic cells, constantly extending and retracting their processes as they contact and functionally regulate neurons and other glial cells. There is far less known about microglia-vascular interactions, particularly under healthy steady-state conditions. Here, we use the male and female mouse cerebral cortex to show that a higher percentage of microglia associate with the vasculature during the first week of postnatal development compared to older ages and the timing of these associations are dependent on the fractalkine receptor (CX3CR1). Similar developmental microglia-vascular associations were detected in the prenatal human brain. Using live imaging in mice, we found that juxtavascular microglia migrated when microglia are actively colonizing the cortex and became stationary by adulthood to occupy the same vascular space for nearly 2 months. Further, juxtavascular microglia at all ages contact vascular areas void of astrocyte endfeet and the developmental shift in microglial migratory behavior along vessels corresponded to when astrocyte endfeet more fully ensheath vessels. Together, our data provide a comprehensive assessment of microglia-vascular interactions. They support a mechanism by which microglia use the vasculature to migrate within the developing brain parenchyma. This migration becomes restricted upon the arrival of astrocyte endfeet when juxtavascular microglia then establish a long-term, stable contact with the vasculature.
Neuroscience, microglia, neuronal cell biology, astrocytes, parenchyma
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 2020.05.25.110908; doi: https://doi.org/10.1101/2020.05.25.110908. Link to preprint on bioRxiv service.
Now published in The Journal of Neuroscience, doi:10.1523/JNEUROSCI.3006-19.2020
Mondo E, Becker SC, Kautzman AG, Schifferer M, Baer CE, Chen J, Huang EJ, Simons M, Schafer DP. (2020). A developmental analysis of juxtavascular microglia dynamics and interactions with the vasculature [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.05.25.110908. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1683
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.