BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) CAN PREVENT APOPTOSIS OF RATCEREBELLAR GRANULE NEURONS IN CULTURE

Cerebellar granule neurons obtained from 9-day-old rats were grown in vitro for 4 days in high K+ (26 mM) medium. The culture medium was the n replaced with that containing low K+ (5 mM) which caused a large num ber of granule neurons to die. The death of granule neurons has been c haracterized as apoptosis. In this study, we investigated the effects of various neurotrophins on neuronal survival using the above system. We found that brain-derived neurotrophic factor (BDNF) and neurotrophi n-4/5 (NT-4/5) but not nerve growth factor (NGF) can protect these neu rons from apoptosis in low K+. Neurotrophin-3 (NT-3) had a small effec t on neuronal survival as reported. To determine whether the granule n eurons respond directly to BDNF, we analyzed the induction of the Fos protein in these neurons. Individual cells that synthesize Fos protein after exposure to neurotrophin can be recognized using antibodies to Fos. Immunocytochemical staining of the cultures demonstrated that a r elatively large number of cerebellar granule neurons showed immunoreac tivity in response to BDNF, but few of them were immunoreactive in the absence of BDNF or in the presence of NGF. Our results suggested that BDNF has a direct effect on mature cerebellar granule neurons and can protect these neurons from apoptosis in low K+.