Objective        To determine the effect of brain-derived neurotrophic factor precursor (proBDNF) on the proliferation and apoptosis of cultured cerebellar granule cells (CGCs) and investigate the underlying mechanism of p75 neurotrophin receptor (p75NTR)/VPS10P-domain family member sortilin pathway.       Methods        CGCs was isolated from 7-day-old transgenic 129SV mice (p75NTR

+/+

and p75NTR

-/-

) and then primarily cultured followed by identification. Then the cells were treated with BSA(10 ng/mL)

proBDNF(10 ng/mL)

proBDNF(10 ng/mL)+sortilin-Fc(20 ng/mL) respectively. Immunofluorescent staining was performed to detect the expression of p75NTR and sortilin in the cultured cells. BrdU and TUNEL positive cells were detected to calculate the proportion of proliferation and apoptosis

respectively.       Results        Primary CGCs were successfully cultured with high purity. Immunofluorescent staining showed a co-expression of p75NTR and sortilin was seen in the cultured p75NTR

+/+

cerebellar neurons

locating in the cell membrane and neurites. proBDNF treatment resulted in the percentage of BrdU positive cells were significantly decreased (P0.01)

but the TUNEL positive cells increased (P0.01) in p75NTR

+/+

cultured CGCs. But these effects were inhibited and neutralized by sortilin-Fc. However

no such change was observed in p75NTR

-/-

cultured CGCs (P0.05).       Conclusion        proBDNF inhibits the proliferation and apoptosis of CGCs probably via forming a triple with p75NTR and sortilin

and exerts a toxic effect on nervous system.