The mechanism of the NgR1 antagonist for promoting the neural precursor cells differentiate into neurons

Abstract

Objective To study the effect of neuronal Nogo-66 receptor (NgR1) antagonist,soluble Nogo-66 receptor (sNgR1-Fc),on promoting the endogenous neural precursor cells (NPCs) differentiating into neurons in order to clarify the mechanism.Methods The cortical infarction was induced by photochemistry,named photothrombotic cortical injury (PCI).Twelve Sprague Dawley rats were randomly divided (random number) into three groups:Sham-operated group,PBS group,and sNgR1-Fc group.PBS (PBS group) or sNgR1-Fc (sNgR1-Fc group) was injected into the lateral ventricle of brain with a minipump.BrdU (Bromodeoxyuridine) was injected into the peritoneal cavity 4-6 days after PCI.The subdentate gyrus zone (SGZ) of brain from sacrificed rat was harvested for Immunohistochemistry to observe the ratio of NeuN +/BrdU + cells 35 days after PCI.Proteins including Nestin、Notch1 and Mash1 were detected by Western Blot.Results The cortical infarction in rat was successfully induced by photochemistry.Thirty-five days after PCI,the BrdU + cells number and theratio of NeuN +/BrdU + in the SGZ of the ipsilateral cerebrum hemisphere with PCI were significantly higher in sNgR1-Fc group than those in PBS group (P ＜ 0.05).The levels of Notch1,Mash1 and Neuro D in the sNgR1-Fc group were significantly higher than those in the PBS group (P ＜ 0.05),which were significantly higher than those in the Sham-operated group.Conclusions sNgR1-Fc could promote the endogenous NPCs differentiating into neurons in a cortical infarction model.The mechanisms may be attributed to the Notch/bHLH (proneural basic helix-loop-helix genes) signaling way. Key words: Nogo-66 receptor; Cortical infarction; Neural precursor cells; Differentiation; Proliferation; Axon ; Regeneration; Signal pathway