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Updated: Jan 3, 2026
Isolation of Mouse Primary Microglia by Magnetic-Activated Cell Sorting in Animal Models of Demyelination
Published on: April 5, 2022
Heterogeneity of microglia and their differential roles in white matter pathology
Janice Lee1, Gen Hamanaka1, Eng H Lo1
1Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Abstract:
Microglia are resident immune cells that play multiple roles in central nervous system (CNS) development and disease. Although the classical concept of microglia/macrophage activation is based on a biphasic beneficial-versus-deleterious polarization, growing evidence now suggests a much more heterogenous profile of microglial activation that underlie their complex roles in the CNS. To date, the majority of data are focused on microglia in gray matter. However, demyelination is a prominent pathologic finding in a wide range of diseases including multiple sclerosis, Alzheimer's disease, and vascular cognitive impairment and dementia. In this mini-review, we discuss newly discovered functional subsets of microglia that contribute to white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on disease type and brain region, especially in white matter. Moreover, in later stages of disease, microglia demonstrate unconventional immuno-regulatory activities such as increased phagocytosis of myelin debris and secretion of trophic factors that stimulate oligodendrocyte lineage cells to facilitate remyelination and disease resolution. Further investigations of these multiple microglia subsets may lead to novel therapeutic approaches to treat white matter pathology in CNS injury and disease.
Insights
Microglia, the CNS immune cells, exhibit diverse activation states beyond simple polarization. New research highlights their crucial roles in white matter diseases, offering potential therapeutic targets.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathology
Background:
- Microglia are key immune cells in the central nervous system (CNS), traditionally viewed with a binary activation model.
- Recent findings reveal a more complex, heterogeneous profile of microglial activation states.
- Most research has focused on gray matter microglia, neglecting their role in white matter pathology.
Purpose of the Study:
- To review newly identified microglial functional subsets involved in white matter responses during CNS diseases.
- To explore the regional and disease-specific heterogeneity of microglia in white matter.
- To discuss the implications of these microglial subsets for therapeutic strategies.
Main Methods:
- Literature review of recent studies on microglial heterogeneity in CNS diseases.
- Analysis of molecular patterns and morphological changes in white matter microglia.
- Examination of immuno-regulatory activities in disease progression.
Main Results:
- Microglia display distinct molecular and morphological profiles in white matter, varying by disease and brain region.
- In later disease stages, microglia exhibit unconventional immune functions, including myelin debris phagocytosis.
- Microglia secrete trophic factors that support oligodendrocyte lineage cells for remyelination.
Conclusions:
- Functional heterogeneity of microglia is critical for understanding white matter responses in CNS diseases.
- Targeting specific microglial subsets may offer novel therapeutic avenues for white matter disorders.
- Further research into these diverse microglial populations is essential for developing effective treatments.
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