Neuregulin Regulates The Formation Of Radial Glial Scaffold In Hippocampal Dentate Gyrus Of Postnatal Rats

In the rodent hippocampus, the radial glial scaffold consists of radial glial cells(RGCs) and plays important roles in neurogenesis in this area after birth. However, themechanisms that maintain and regulate the radial glial scaffold in the postnatal dentategyrus (DG) area remain elusive. It is therefore important to understand the mechanismabout regulating radial glial scaffold and the factors involving, especially after birth.An EGF family factor, Neuregulin (NRG) modulates the establishment of radialglia and maintains the radial glial fiber elongation in the rat cerebral cortex andcerebellum. It indicates that NRG might be an important factor in regulating radial glialscaffold. In this work, using a cultured rat hippocampus slice system, we found radialglial scaffold existing in the hippocampus slice before and after culture, and NRGreceptor ErbB4 expressing in the radial glial cells.The results indicate that NRG promote the bromodeoxyuridine (BrdU)incorporation in the cultured hippocampus slices but not affect the cell apoptosisprogram. U0126, PD98059, inhibitors of MAPK pathway;and LY294002, Wortmann,inhibitors of PI3-Kinase pathway, both inhibited BrdU incorporation induced by NRG,suggesting that the MAPK pathway and PI3-Kinase pathways are required forNRG-induced cell proliferation. Then the result shows these BrdU incorporating cellsare Nestin+ radial glial cells. Using the radial glial specifically expressing Vimentinprotein, we found NRG promote the Vimentin+ radial glial cells in hippocampus dentategyrus.Ab-3, a inhibitor to block the binding of NRG to its receptor ErbB4, inhibit theradial glial cells proliferation induced by NRG. The immonohistochemistry experimentsresults from cultured hippocampus slices and cultured dentate gyrus explants indicatedthat endogenous NRG maintain the radial glial cells morphology and fiber elongation inthe dentate gyrus EGL area. The inhibitor Ab-3 could disrupt the normal structure ofradial glial scaffold by destroying the undifferentiated morphology of radial glial cellswith long fiberThese findings suggests an important role of NRG in maintaining the functionalradial glial scaffold existing by regulating and maintaining the normal quantity andmorphology of radial glial cells in postnatal hippocampus dentate gyrus .