A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

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.

The Indispensable Roles of Microglia and Astrocytes during Brain Development

“…A subset of microglia was further shown to produce nitric oxide (NO), a signaling molecule that regulates the developmental switch from neuro- to astrogenesis and astroglial maturation (Peunova and Enikolopov, 1995; Béchade et al, 2011). Interestingly, apart from their effect on developmental neurogenesis, microglia can influence adult hippocampal neurogenesis by phagocytosis of apoptotic cells (Sierra et al, 2010) and are also able to provide trophic support to new adult born neurons in the hippocampus and SVZ (for review see Gemma and Bachstetter, 2013; Ribeiro Xavier et al, 2015). It is thus likely that the mechanisms microglia use to affect developmental neuro- and astrogenesis, can also be used to influence SVZ and hippocampal neurogenesis in the adult (Aarum et al, 2003; Kanski et al, 2014; Valero et al, 2016).…”

Cannabinoid Type-2 Receptor Drives Neurogenesis and Improves Functional Outcome After Stroke

“…Specifically, it has been described that microglia at the SVZ and the rostral migratory stream, with features of alternatively activated microglia, seems to support both survival and migration of newly generated neuroblasts through the rostral migratory stream to the olfactory bulb. 48 In our experimental setting, endogenous CB2R activation might underlie the skewing of microglia toward a phenotype that fosters the migration of neuroblasts, an effect that deserves further studies.…”

“…Однако нельзя исключить, что и другие клетки могут способствовать этому промигрирующему эффекту in vivo. В частности, было описано, что микроглия в СВЗ и ростральном миграционном тракте с особенностями альтернативно активированной микроглии, по-видимо-му, поддерживает выживание и миграцию вновь образо-ванных нейробластов через ростральный миграционный тракт в обонятельную луковицу [48]. В наших экспери-ментальных условиях эндогенная активация CB2R может лежать в основе трансформации микроглии к фенотипу, способствующему миграции нейробластов, и этот вопрос заслуживает дальнейшего изучения.…”

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

“…Recent data have established that mouse microglia possess a unique transcriptional and proteomic signature [20,21], including the unique expression of purinergic receptor P2Y12 [20,22] and transmembrane protein 119 [23] on the cell surface, now enabling specific labelling with antibodies. Evidence also indicates there are likely to be several heterogeneous subsets of microglia with region-specific functions, with a recent report highlighting a unique subset of fractalkine receptor (CX3CR1)-positive microglia present in the subventricular zone (SVZ), rostral migratory stream, and olfactory bulb that lacked ‘typical’ microglial markers Iba1, isolectin B4, and CD68, and appeared to be involved in the migration and integration of adult SVZ-derived neural progenitors into the olfactory bulb [24]. Other researchers have also used bone marrow chimeras and promoter-driven transgenic animals to label resident and infiltrating cells separately, and have found that in many conditions, the two subsets of cells vary considerably in their ability to phagocytose pathological deposits of protein, recruit other immune cells via antigen presentation, and contribute to pathology via production of neurotoxic substances [6].…”

“…Therefore readers are strongly encouraged to evaluate the literature regarding neuro-inflammation and microglial activation with care, and to refrain from equating microglia and CNS macrophages in their own research. This can now be achieved relatively easily, as many reporter systems are available [10], and the transcriptional profiles of the two major subsets are well characterized [22,23,24,34]. Additionally, novel methods of depleting specific subsets of cells are under development [199], which may assist with the functional characterization of the heterogeneous subsets of microglia and other myeloid cells without confounding effects of irradiation on brain tissue, for example [200].…”