Mj. Marti et al., EARLY DEVELOPMENTAL DESTRUCTION OF TERMINALS IN THE STRIATAL TARGET INDUCES APOPTOSIS IN DOPAMINE NEURONS OF THE SUBSTANTIA-NIGRA, The Journal of neuroscience, 17(6), 1997, pp. 2030-2039
Many developing neural systems with peripheral projections depend on t
heir target for trophic support during a critical period of natural ce
ll death. Much less is known about central systems. That dopaminergic
neurons of the substantia nigra may depend on their target, the striat
um, during development is suggested by the presence of a natural apopt
otic cell death event in these neurons that can be augmented by an ear
ly developmental axon-sparing striatal injury, To further assess the t
arget dependence of these neurons, we have used the selective neurotox
in B-hydroxydopamine to lesion their terminals within the striatum dur
ing development, while sparing intrinsic striatal target neurons. This
lesion results in an induction of apoptotic cell death in phenotypica
lly defined dopaminergic neurons that appears on the third postlesion
day and persists until the tenth, This inducibility of cell death is d
ependent on developmental age: it is most marked before postnatal day
(PND) 14. As late as PND42, inducibility is still detectable but much
less so, In addition, at day 42 the morphology of cell death changes a
nd becomes nonapoptotic in some cells. We conclude that terminal injur
y during a critical period of postnatal development, like axon-sparing
target injury, induces augmented apoptotic death in mesencephalic dop
aminergic neurons. These results suggest that these neurons have a per
iod of target dependence. Regulation of this dependence is likely to i
nfluence the mature adult number of dopaminergic neurons.