Reciprocal developmental changes in the roles of Bcl-w and Bcl-xL in regulating sensory neuron survival

We have compared the roles of two anti-apoptotic members of the Bcl2 family, Bcl-w and Bcl-x(L), in regulating the survival of sensory neurons during development. We used microinjection to introduce expression plasmids containing Bcl-w and Bcl-x(L) cDNAs in the sense and antisense orientations into the nuclei of BDNF-dependent nodose neurons and NGF-dependent trigeminal neurons at stages during and after the period of naturally occurring neuronal death. Whilst overexpression of either protein promoted neuronal survival in the absence of neurotrophins and microinjection of antisense constructs reduced neuronal survival in the presence of neurotrophins, the magnitude of these effects changed with age. Whereas Bcl-w overexpression became more effective in promoting neuronal survival with age, Bcl-x(L) overexpression became less effective, and whereas antisense Bcl-w became much more effective in killing neurotrophin-supplemented neurons with age, antisense Bcl-x(L) became much less effective in killing these neurons. There was a marked increased in Bcl-w mRNA and Bcl-w immunoreactive neurons and a decrease in Bcl-x(L) mRNA and Bcl-x(L) immunoreactive neurons in the trigeminal and nodose ganglia over this period of development. Our results demonstrate that both Bcl-w and Bcl-x(L )play an important anti-apoptotic role in regulating the survival of NGF- and BDNF-dependent neurons, and that reciprocal changes occur in the relative importance of these proteins with age. Whereas Bcl-x(L) plays a more important role during the period of naturally occurring neuronal death, Bcl-w plays a more important role at later stages.