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A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone
Anna L Ribeiro Xavier1, Benjamin T Kress2, Steven A Goldman3
1Laboratório de Neuroanatomia Celular, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902 Brazil, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642, and.
Abstract:
Microglia are involved in synaptic pruning both in development and in the mature CNS. In this study, we investigated whether microglia might further contribute to circuit plasticity by modulating neuronal recruitment from the neurogenic subventricular zone (SVZ) of the adult mouse striatum. We found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low expression of purinoceptors and lack of ATP-elicitable chemotaxis. Furthermore, the in vivo depletion of these microglia hampered the survival and migration of newly generated neuroblasts through the RMS to the olfactory bulb. SVZ and RMS microglia thus appear to comprise a functionally distinct class that is selectively adapted to the support and direction of neuronal integration into the olfactory circuitry. Therefore, this unique microglial subpopulation may serve as a novel target with which to modulate cellular addition from endogenous neural stem and progenitor cells of the adult brain.
Significance Statement:
Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural circuitry sculpture. Here, we addressed microglial functions in the subventricular zone (SVZ), the major postnatal neurogenic niche. Our results depict microglia as a conspicuous component of SVZ and its anterior extension, the rostral migratory stream, a pathway used by neuroblasts during their transit toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal progenitor survival and migration in the mammalian brain.
Insights
Specialized microglia in the adult brain support new neuron survival and migration. These distinct immune cells in the subventricular zone (SVZ) and rostral migratory stream (RMS) are key for olfactory circuit integration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are immune cells in the central nervous system (CNS) involved in synaptic pruning.
- The subventricular zone (SVZ) is a neurogenic niche in the adult brain where new neurons are generated.
Purpose of the Study:
- To investigate the role of microglia in neuronal recruitment from the adult mouse SVZ.
- To determine if microglia modulate the survival and migration of neuroblasts.
Main Methods:
- Characterization of microglia in the SVZ and rostral migratory stream (RMS).
- Analysis of microglial phenotype, including purinoceptor expression and chemotaxis.
- In vivo depletion of microglia to assess effects on neuroblast survival and migration.
Main Results:
- Microglia in the SVZ/RMS exhibit a distinct phenotype, with low purinoceptor expression and lack of ATP-elicitable chemotaxis.
- Depletion of these microglia impaired the survival and migration of new neuroblasts.
- SVZ/RMS microglia are crucial for directing neuronal integration into olfactory circuitry.
Conclusions:
- Microglia in the SVZ and RMS are a functionally distinct population.
- These microglia support and direct the integration of new neurons into the olfactory system.
- This microglial subpopulation represents a potential target for modulating adult neurogenesis.
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