Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis

By Amanda Sierra, J. Encinas, J. Deudero, J. H. Chancey, G. Enikolopov, Linda Overstreet-Wadiche, S. Tsirka, M. Maletić-Savatić. 2010

1,614 citations recorded by the source corpus.

Summary In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the hippocampal circuitry as mature neurons at the end of a four-week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in the first one to four days of their life, during the transition from amplifying neuroprogenitors to neuroblasts. These apoptotic newborn cells are rapidly cleared out through phagocytosis by unchallenged microglia present in the adult SGZ niche. Phagocytosis by the microglia is efficient and undeterred by increased age or inflammatory challenge. Our results suggest that the main critical period of newborn cell survival occurs within a few days of birth and reveal a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.

Subfields: Developmental Neuroscience, Immunology, Neurology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “Neural progeny survival exhibits two critical periods (Figure 3), one at the intermediate progenitor and neuroblast stage (Platel et al., 2010; Sierra et al., 2010) and one at the immature neuron integration stage (Mouret et al., 2008; Tashiro et al., 2006).”
Microglia regulate the number of neural precursor cells in the developing cerebral cortex (2013, background): “, 2012), and phagocytose newborn neurons in the subgranular zone of the adult hippocampus (Sierra et al., 2010).”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “During this early stage of development, a significant percentage of newborn progeny is eliminated through apoptosis and microglia-mediated phagocytosis (Sierra et al., 2010).”
The Role of Microglia in the Healthy Brain (2011, background): “Moreover, although bacterial lipopolisaccharides (LPS) induced apoptosis in the SGZ (Sierra et al., 2010), it remains unknown whether the proapoptotic effect of LPS is due to excitotoxic properties of proinflammatory cytokines (Pickering et al., 2005) or to direct activation of microglial phagocytos”
Microglial cell origin and phenotypes in health and disease (2011, background): “The majority of neuroblasts that are generated in the subgranular zone of the dentate gyrus undergo apoptosis, and steady-state microglia phagocytose these apoptotic cells, with this activity being most prominent in young (1-month-old) mic”
In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics (2011, positive): “Consistent with a recent finding of significant cell death during the transition from IPCs to neuroblasts in adult hippocampal neurogenesis (Sierra et al., 2010), all large clones observed in this study contained IPCs.”
Microglial M1/M2 polarization and metabolic states (2016, background): “Similar to macrophages, microglia mount an immune response to pathogens, monitor for tissue changes and maintain tissue homeostasis by clearing pathogens, dying cells, debris or aberrant proteins (Gehrmann et al., 1995; Bruce-Keller, 1999; Stevens et al., 2007; Wake et al., 2009; Nagamoto-Combs et a”
The biphasic function of microglia in ischemic stroke (2017, positive): “In aged or LPSstimulated rat brain, inhibiting microglia enhanced the number of new born cells and promoted neurogenesis in the sub granular zone (Sierra et al., 2010).”
Microglia: new roles for the synaptic stripper. (2013, positive): “…and pathological phagocytosis showmorphological specificity: the phagocytosis of synaptic material or apoptotic cells is performed without affecting the ramifiedmicroglial phenotype, bymicroglial processes or ‘‘en passant’’ branches forming ‘‘ball-and-chain’’ structures (Sierra et al., 2010).”