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Updated: Aug 12, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Turnover of resident microglia in the normal adult mouse brain
L J Lawson1, V H Perry, S Gordon
1Department of Pharmacology, University of Oxford, U.K.
Abstract:
We undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [3H]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 +/- 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 +/- 0.052%. From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: (i) resident microglia can synthesise DNA and go on to divide in situ; (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia.
Insights
Resident microglia, the brain's immune cells, can divide in place and are also replenished by circulating monocytes. This steady-state turnover supports the "Trojan Horse" hypothesis for central nervous system infections.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells residing in the central nervous system.
- Understanding microglia turnover is crucial for neuroinflammatory and neurodegenerative disease research.
- The origin of microglia in steady-state conditions has been a long-standing question.
Purpose of the Study:
- To investigate whether microglia, the resident macrophages of the central nervous system, undergo turnover in a steady-state.
- To determine the contribution of local proliferation versus circulating monocytes to the microglia pool.
Main Methods:
- Utilized immunohistochemistry for F4/80 (a macrophage marker) combined with [3H]thymidine incorporation and autoradiography in adult mice.
- Analyzed double-labeled cells at various time points post-isotope administration.
- Assessed cell morphology, mitotic figures, and cell pairing to identify dividing and newly recruited cells.
Main Results:
- Detected double-labeled cells (indicating DNA synthesis and presence of microglia) in the brain shortly after isotope administration.
- Observed an increase in double-labeled cells at longer survival times, with morphological evidence of division and differentiation.
- Demonstrated that resident microglia can synthesize DNA and divide in situ, with cells also recruited from the circulating monocyte pool.
Conclusions:
- Resident microglia possess the capacity for in situ DNA synthesis and cell division.
- Circulating monocytes are recruited across the intact blood-brain barrier and differentiate into microglia.
- Both local proliferation and monocyte recruitment contribute approximately equally to the steady-state turnover of microglia.
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