Abstract
In mammalian species, including humans, the hippocampal dentate gyrus (DG) is a primary region of adult neurogenesis. Aberrant adult hippocampal neurogenesis is associated with neurological pathologies. Understanding the cellular mechanisms controlling adult hippocampal neurogenesis is expected to open new therapeutic strategies for mental disorders. Microglia is intimately associated with neural progenitor cells in the hippocampal DG and has been implicated, under varying experimental conditions, in the control of the proliferation, differentiation and survival of neural precursor cells. But the underlying mechanisms remain poorly defined. Using fluorescent in situ hybridization we show that microglia in brain express the ADP-activated P2Y13 receptor under basal conditions and that P2ry13 mRNA is absent from neurons, astrocytes, and neural progenitor cells. Disrupting P2ry13 decreases structural complexity of microglia in the hippocampal subgranular zone (SGZ). But it increases progenitor cell proliferation and new neuron formation. Our data suggest that P2Y13 receptor-activated microglia constitutively attenuate hippocampal neurogenesis. This identifies a signaling pathway whereby microglia, via a nucleotide-mediated mechanism, contribute to the homeostatic control of adult hippocampal neurogenesis. Selective P2Y13R antagonists could boost neurogenesis in pathological conditions associated with impaired hippocampal neurogenesis.
Highlights
Microglia have long been known as major orchestrators of the brain inflammatory response
Double labeling for the microglia/macrophage-specific ionized calcium binding adaptor molecule 1 (Iba1) shows that P2ry13 mRNA is located in microglia (Figure 1A)
The results reported so far imply that microglia via the P2Y13R impacts neurogenesis in the dentate gyrus (DG)
Summary
Microglia have long been known as major orchestrators of the brain inflammatory response. They actively move to sites of damage and engulf and eliminate neural debris. They continuously survey their cellular environment and regulate neuronal survival, migration of neurons, axonal growth, pruning of supernumerary synapses, and functional maturation of developing synapses (Nayak et al, 2014; Sierra et al, 2014). The role of microglia in the control of developmental and adult neuron formation has recently received increasing attention (Gemma and Bachstetter, 2013). Microglia is intimately associated with neural progenitor cells in the adult hippocampal dentate gyrus (DG) and has been implicated in the control of neurogenesis.
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