ROLE OF BCL-2 IN THE SURVIVAL AND FUNCTION OF DEVELOPING AND MATURE SYMPATHETIC NEURONS

Sympathetic neurons, when placed in culture during the period of natur ally occurring cell death, will die by apoptosis when deprived of nerv e growth factor (NGF). In this system, the mRNA levels of the BCL-2 fa mily members decrease after NGF deprivation and during apoptosis. Symp athetic neurons from BCL-2-deficient mice died more rapidly after NGF deprivation than neurons from wild-type littermates. Sympathetic neuro ns of adult animals are relatively independent of NGF for survival. If sympathetic neurons are maintained in vitro for several weeks, loss o f acute trophic factor dependence develops with a time course similar to that seen in the intact animal. Examination of neurons from BCL-2-d eficient mice showed that BCL-2 expression is not required for the dev elopment of trophic factor independence. Therefore, BCL-2 is an import ant regulator of the survival of sympathetic neurons after NGF depriva tion during the period of naturally occurring programmed neuronal deat h, but BCL-2 is not involved in the development of trophic factor inde pendence in mature sympathetic neurons.