Brain-derived neurotrophic factor suppresses programmed death of cerebellar granule cells through a posttranslational mechanism.

Abstract

Cerebellar granule cells isolated from 7-d-old rats have been shown to die in vitro unless they are continuously exposed to elevated K+ (25 mM). Here we have characterized this neuronal death, and examined whether its major features are shared with those of sympathetic neurons following nerve growth factor (NGF) deprivation. Granule cells underwent active cell death accompanied by morphological features of apoptosis. Brain-derived neurotrophic factor (BDNF), but not NGF, was capable of preventing this neuronal death by acting posttranslationally. Moreover, semiquantitative RT-PCR, Northern blot, and immunoblot analyses showed that trkB, the signal-transducing receptor for BDNF, was upregulated during neuronal death of granule cells in vitro. These results extend recent findings for the role of BDNF in granule cell development, and suggest that BDNF plays a pivotal role on the regulation of the neuronal death/survival of granule cells.