proBDNF Attenuates Hippocampal Neurogenesis and Induces Learning and Memory Deficits in Aged Mice

Mature brain-derived neurotrophic factor has shown promotive effect on neural cells in rodents, including neural proliferation, differentiation, survival, and synaptic formation. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has been emerging as a differing protein against its mature form, for its critical role in aging process and neurodegenerative diseases. In the present study, we investigated the role of proBDNF in neurogenesis in the hippocampal dentate gyrus of aged mice and examined the changes in mice learning and memory functions. The results showed that the newborn cells in the hippocampus revealed a significant decline in proBDNF-treated group compared with bovine serum albumin group, but an elevated level in anti-proBDNF group. During the maturation period, no significant change was observed in the proportions of phenotype of the newborn cells among the three groups. In water maze, proBDNF-treated mice had poorer scores in place navigation test and probe test, compared with those from any other group. Thus, we conclude that proBDNF attenuates neurogenesis in the hippocampus and induces the deficits in learning and memory functions of aged mice.