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Updated: Dec 8, 2025
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Effects of long-term and brain-wide colonization of peripheral bone marrow-derived myeloid cells in the CNS
Lindsay A Hohsfield1, Allison R Najafi1, Yasamine Ghorbanian2,3
1Department of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 92697-4545, USA.
Background:
Microglia, the primary resident myeloid cells of the brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfunction has been implicated in a number of central nervous system (CNS) disorders, thus developing tools to manipulate and replace these myeloid cells in the CNS is of therapeutic interest.
Methods:
Using whole body irradiation, bone marrow transplant, and colony-stimulating factor 1 receptor inhibition, we achieve long-term and brain-wide (~ 80%) engraftment and colonization of peripheral bone marrow-derived myeloid cells (i.e., monocytes) in the brain parenchyma and evaluated the long-term effects of their colonization in the CNS.
Results:
Here, we identify a monocyte signature that includes an upregulation in Ccr1, Ms4a6b, Ms4a6c, Ms4a7, Apobec1, Lyz2, Mrc1, Tmem221, Tlr8, Lilrb4a, Msr1, Nnt, and Wdfy1 and a downregulation of Siglech, Slc2a5, and Ccl21a/b. We demonstrate that irradiation and long-term (~ 6 months) engraftment of the CNS by monocytes induces brain region-dependent alterations in transcription profiles, astrocytes, neuronal structures, including synaptic components, and cognition. Although our results show that microglial replacement with peripherally derived myeloid cells is feasible and that irradiation-induced changes can be reversed by the replacement of microglia with monocytes in the hippocampus, we also observe that brain-wide engraftment of peripheral myeloid cells (relying on irradiation) can result in cognitive and synaptic deficits.
Conclusions:
These findings provide insight into better understanding the role and complexity of myeloid cells in the brain, including their regulation of other CNS cells and functional outcomes.
Insights
Replacing brain microglia with peripheral monocytes is feasible but can cause cognitive deficits. This study explores myeloid cell function in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are crucial brain myeloid cells for homeostasis and response to injury.
- Microglial dysfunction is linked to central nervous system (CNS) disorders, highlighting therapeutic interest in myeloid cell manipulation.
- Developing tools to replace CNS myeloid cells is a key therapeutic goal.
Purpose of the Study:
- To investigate the long-term effects of replacing microglia with peripheral myeloid cells in the brain.
- To identify molecular signatures associated with monocyte engraftment in the CNS.
- To evaluate the impact of myeloid cell colonization on brain structure, function, and cognition.
Main Methods:
- Utilized whole body irradiation and bone marrow transplant to achieve brain-wide engraftment of peripheral monocytes.
- Employed colony-stimulating factor 1 receptor inhibition.
- Analyzed transcriptional profiles, neuronal structures, and cognitive function following monocyte colonization.
Main Results:
- Identified a specific monocyte gene signature upon CNS engraftment.
- Demonstrated brain region-dependent alterations in transcription, astrocytes, and synaptic components.
- Observed cognitive and synaptic deficits following broad peripheral myeloid cell engraftment, despite successful hippocampal microglial replacement.
Conclusions:
- Microglial replacement with peripherally derived monocytes is achievable.
- Brain-wide engraftment of peripheral myeloid cells can lead to detrimental cognitive and synaptic effects.
- Findings enhance understanding of myeloid cell roles and regulation within the CNS.
