rPGRN promotes neurite outgrowth and branching in primary neurons. (A) (A,B) Bar graph quantification of total neurite outgrowth (A) and branching (B) of WT hippocampal neurons exposed to rPGRN increasing 25, 125, 625 nM doses of His-rPGRN (nM doses correspond to 2,10, 50 ug/mL concentrations respectively). All doses normalized to WT non-treated cultures. (C,D) Bar graph quantification of normalized total neurite outgrowth (C) and branching (D) in of Grn−/− hippocampal neurons exposed to rPGRN. Grn−/− cultures were normalized to WT non-treated cultures. (E) Western blot analysis reveals PGRN cleavage in Grn−/− hippocampal cultures treated with 125 nM rPGRN-His at increasing time points. Note cleavage of PGRN after only one hour. Data is presented as the mean ± SEM. **p < 0.01.