Abstract
Microglia are reported to have significant roles in regulating normal mammalian adult neurogenesis. There are two neurogenic niches in the adult mammal brain: the subgranular zone (SGZ) in the hippocampus, and the subventricular zone (SVZ), which makes up the lining of the lateral ventricles. While the microglia interactions on adult neurogenesis in the hippocampus have been characterized, the SVZ niche is not as well investigated. The SVZ niche is unique in that the newborn neurons migrate a much longer distance through multiple brain structures compared to newborn neurons in the hippocampus, making it more difficult to fully characterize how microglia influence this process. To examine the SVZ niche and migration pathway, we used the colony stimulating factor 1 receptor (CSF1R) antagonist PLX5622, which promotes brain wide microglia ablation. Microglia ablation resulted in no changes in the numbers of neural stem cells (NSCs), transient amplifying cells, and neuroblasts. Microglia ablation in the olfactory bulb (OB) was decreased compared to the SVZ. CSF1R inhibition had no effect on the ability of microglia to proliferate. Thus, our data suggest that microglia are not required for normal functioning SVZ adult neurogenesis.
Highlights
In the adult mammalian brain, new neurons are continuously born from neural stem cells (NSCs; reviewed in Bond et al, 2015)
We find that microglia are not required for normal proliferation and differentiation in the adult subventricular zone (SVZ) and rostral migratory stream (RMS), and we report that colony stimulating factor 1 receptor (CSF1R) inhibition via PLX5622 does not affect microglia proliferation rates
At 14 days (14d) of treatment, there were higher numbers of microglia in the olfactory bulb (OB) compared to the SVZ in both control and PLX5622 treated mice, and in the RMS compared to the SVZ in control mice (Figure 1C)
Summary
In the adult mammalian brain, new neurons are continuously born from neural stem cells (NSCs; reviewed in Bond et al, 2015). Genetic ablation of TAM receptor kinases Mer and Axl, which are involved with phagocytosis of apoptotic cells, result in an increase of apoptotic cells in the SVZ and RMS (Scott et al, 2001; Fourgeaud et al, 2016). We use a different microglial inhibitor, PLX5622, which does not act on c-Kit, and has been reported to yield ∼90% microglial ablation (Acharya et al, 2016; Walter and Crews, 2017; Nissen et al, 2018; Seitz et al, 2018; Unger et al, 2018) It is delivered orally in the mouse chow, and this non-invasive delivery methods is preferred to local injections or infusion of other compounds that result in (minimal) mechanical injury in the tissue and accompanying microglial activation (Torres et al, 2016). We find that microglia are not required for normal proliferation and differentiation in the adult SVZ and RMS, and we report that CSF1R inhibition via PLX5622 does not affect microglia proliferation rates
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