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What Do Microglia Really Do in Healthy Adult Brain?
Marcus Augusto-Oliveira1,2, Gabriela P Arrifano3,4, Amanda Lopes-Araújo5
1Laboratório de Farmacologia Molecular (Instituto de Ciências Biológicas), Universidade Federal do Pará, Belém 66075-110, Brasil. marcusoliveira@globo.com.
Abstract:
Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease.
Insights
Microglia, the brain's immune cells, are crucial for maintaining brain health and cognitive function in adults, not just during disease. Their role extends beyond inflammation to actively support brain homeostasis and learning.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, originating from yolk sac-primitive macrophages, self-renew throughout adulthood.
- While their role in brain pathology is well-studied, their function in the healthy adult brain remains less understood.
- Astrocytes and oligodendrocytes are recognized for maintaining brain homeostasis and modulating neuronal function.
Purpose of the Study:
- To explore the underappreciated role of microglia in the healthy adult brain.
- To reposition microglia as key contributors to cognitive processes and brain homeostasis.
- To highlight emerging evidence on microglia's influence on adult neurogenesis.
Main Methods:
- Review of existing literature on microglia function.
- Analysis of studies utilizing microglial depletion assays and conditional mutants.
- Examination of research investigating microglia's impact on cognition, learning, and neurogenesis.
Main Results:
- Absence of microglia can lead to developmental cognitive deficits, with less pronounced effects in adults.
- Emerging evidence indicates microglia significantly influence adult cognition, learning, and potentially adult neurogenesis.
- Microglia actively contribute to maintaining brain homeostasis in healthy adults.
Conclusions:
- Microglia are essential for maintaining brain homeostasis and cognitive function in healthy adult brains.
- Their role extends beyond neuroinflammation to actively support brain health and learning.
- Further research is needed to fully elucidate the multifaceted functions of microglia in the adult brain.
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