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Updated: Jun 22, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development
Mariya Hristova1, Daniel Cuthill, Virginia Zbarsky
1Department of Obstetrics and Gynecology, EGA Institute of Women's Health, University College London, London, United Kingdom.
Abstract:
Brain microglia are related to peripheral macrophages but undergo a highly specific process of regional maturation and differentiation inside the brain. Here, we examined this deactivation and morphological differentiation in cerebral cortex and periventricular subcortical white matter, the main "fountain of microglia" site, during postnatal mouse development, 0-28 days after birth (P0-P28). Only macrophages in subcortical white matter but not cortical microglia exhibited strong expression of typical activation markers alpha5, alpha6, alphaM, alphaX, and beta2 integrin subunits and B7.2 at any postnatal time point studied. White matter phagocyte activation was maximal at P0, decreased linearly over P3 and P7 and disappeared at P10. P7 white matter phagocytes also expressed high levels of IGF1 and MCSF, but not TNFalpha mRNA; this expression disappeared at P14. This process of deactivation followed the presence of ingested phagocytic material but correlated only moderately with ramification, and not with the extent of TUNEL+ death in neighboring cells, their ingestion or microglial proliferation. Intravenous fluosphere labeling revealed postnatal recruitment and transformation of circulating leukocytes into meningeal and perivascular macrophages as well as into ramified cortical microglia, but bypassing the white matter areas. In conclusion, this study describes strong and selective activation of postnatally resident phagocytes in the P0-P7 subcortical white matter, roughly equivalent to mid 3rd trimester human fetal development. This presence of highly active and IGF1- and MCSF-expressing phagocytes in the neighborhood of vulnerable white matter could play an important role in the genesis of or protection against axonal damage in the fetus and premature neonate.
Insights
Newly born brain phagocytes in mouse white matter show high activation and specific markers, crucial for early development and potential protection against axonal damage in newborns.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, the brain's resident immune cells, originate from peripheral macrophages but mature uniquely within the central nervous system.
- Understanding microglia's early postnatal development is key to comprehending brain development and disease susceptibility.
Purpose of the Study:
- To investigate the deactivation and morphological differentiation of microglia in specific brain regions during early postnatal development in mice.
- To characterize the activation status and molecular profiles of phagocytes in the subcortical white matter, a critical developmental site.
Main Methods:
- Comparative analysis of microglia and macrophages in the cerebral cortex and subcortical white matter from postnatal day 0 to 28 in mice.
- Assessment of activation markers (integrin subunits, B7.2), growth factors (IGF1, MCSF), and inflammatory cytokines (TNFα).
- Tracking of circulating leukocyte recruitment using intravenous fluosphere labeling.
Main Results:
- Subcortical white matter phagocytes exhibited strong activation markers from P0 to P10, peaking at P0 and decreasing thereafter.
- These phagocytes expressed high levels of IGF1 and MCSF at P7, indicating a supportive role.
- Cortical microglia showed lower activation, and circulating leukocytes preferentially populated meningeal and perivascular spaces, bypassing white matter.
Conclusions:
- Postnatal resident phagocytes in mouse subcortical white matter display significant, region-specific activation during the first postnatal week, analogous to late-term human fetal development.
- The presence of these activated, IGF1- and MCSF-expressing phagocytes near vulnerable white matter suggests a critical role in regulating axonal integrity in fetuses and premature neonates.
