Microglia In The Neurogenic Niche Are Influenced By CX3CL1 To Promote Neurogenesis

Most neuropsychiatric diseases are accompanied with neuronal damage and disruption of neural circuits,which points out that recovering these damages with new neurons as a possible treatment.Engrafting neurons or neural stem cells would cause a serious risk of rejection,thus it’s better to mobilize new neuron generation of patients’ own bodies.Normally,most neural stem/progenitor cells(NSPCs)would decease after development,therefore in the brains of adult mammals,neurons are replaced slowly,for there’re only a few NSPCs lying quiescently in discrete regions of the brain and only being activated facing stimulation.The subventricular zone and the subgranular zone are the major regions which still have neurogenesis ability in adult mammals.New born neurons derived from NSPCs proliferation and differentiation in these regions,would migrate to the olfactory bulb through the rostral migration stream and to the granular zone in the hippocampus,respectively.As the residential macrophages in the central nervous system,microglia exist throughout the brain.In the neurogenic regions where adult neurogenesis happens,microglia entangle with neural progenitor/stem cells(NSPCs),which indicates a possible intricate interaction between these two types of cells.Observations of microglia in different brain regions show that microglia there have distinct density and morphology.The subgranular zone in the hippocampus is important for adult neurogenesis in mammals,and NSPCs in this region may require some special qualities of microglia to support their functions.We hypothesis that NSPCs express CX3CL1 to induce microglia to help neurogenesis.We first explored the hypothesis using in vitro experiments.The results show that NSPCs can express CX3CL1,and the ligand can influence microglial migration and morphology.Then we introduce the Chronic Mild Stress(CMS)model,in which neurogenesis is disrupted and microglia are over-activated.To comprehend effects of CX3CL1 on over-activated microglia,we injected CX3CL1 recombinase protein into the hippocampus of CMS mice.The results show that CMS mice receiving injection have recovered from stress behaviors,and microglial density and morphology have been changed.Overall,we’ve explored differences between microglia in neurogenic regions and non-neurogenic regions,and investigated how CX3CL1,which can be expressed by NSPCs,influenced microglia in vitro.And we’ve found out that CX3CL1 could regulate microglia in neurogenic regions in a CMS model,which leads to recovery of stress behaviors.