OBJECTIVE: To explore the effects of proBDNF on cell proliferation and differentiation in hippocampal dentate gyrus in Alzheimer' disease (AD) rat model. METHODS: The AD rat model was established. Alzet osmotic minipumps were connected to right hippocampus of AD rat and filled with proBDNF, sheep antibody to proBDNF or normal sheep serum respectively. Rats received the injection for 14 days at the speed of 0.5 microl/h. 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg, ip) was injected twice daily for 14 days. BrdU immunohistochemistry was processed to determine the number of newly generated cells. To examine the phenotype of newly generated cells, immunofluorescent triple labeling was conducted to colocalize BrdU-positive cells with rabbit anti-doublecortin (DCX) or mouse anti-glial fibrillary acid protein (GFAP). RESULTS: proBDNF group had fewer BrdU positive cells in dentate gyrus (P < 0.01), while anti-proBDNF group had more BrdU positive cells (P < 0.01) as compared with control group respectively. Immunofluorescent triple labeling showed that there was no phenotypic difference of BrdU positive cells between each group. CONCLUSION: proBDNF can suppress the proliferation of hippocampal neuron in dentate gyrus in AD rats while anti-proBDNF has the opposite effect. These findings suggest that promoting the hippocampal neurogenesis by blocking the functions of endogenous proBDNF may be a potential therapeutic strategy for AD.
OBJECTIVE: To explore the effects of proBDNF on cell proliferation and differentiation in hippocampal dentate gyrus in Alzheimer' disease (AD) rat model. METHODS: The ADrat model was established. Alzet osmotic minipumps were connected to right hippocampus of ADrat and filled with proBDNF, sheep antibody to proBDNF or normal sheep serum respectively. Rats received the injection for 14 days at the speed of 0.5 microl/h. 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg, ip) was injected twice daily for 14 days. BrdU immunohistochemistry was processed to determine the number of newly generated cells. To examine the phenotype of newly generated cells, immunofluorescent triple labeling was conducted to colocalize BrdU-positive cells with rabbit anti-doublecortin (DCX) or mouseanti-glial fibrillary acid protein (GFAP). RESULTS: proBDNF group had fewer BrdU positive cells in dentate gyrus (P < 0.01), while anti-proBDNF group had more BrdU positive cells (P < 0.01) as compared with control group respectively. Immunofluorescent triple labeling showed that there was no phenotypic difference of BrdU positive cells between each group. CONCLUSION: proBDNF can suppress the proliferation of hippocampal neuron in dentate gyrus in ADrats while anti-proBDNF has the opposite effect. These findings suggest that promoting the hippocampal neurogenesis by blocking the functions of endogenous proBDNF may be a potential therapeutic strategy for AD.