Synuclein expression is decreased in rat substantia nigra following induction of apoptosis by intrastriatal 6-hydroxydopamine.

We have previously shown that synuclein is upregulated in the substantia nigra following developmental lesion of the target striatum. In this model, synuclein is preferentially expressed in normal-appearing neurons, rather than those which undergo apoptosis. It has been proposed, however, that synuclein may mediate apoptosis in other contexts, such as that induced by neurotoxins. To examine this possibility, we have studied a model in which apoptosis is induced in dopamine neurons by intrastriatal injection of 6-hydroxydopamine. In this model synuclein mRNA and protein expression are not upregulated at any time point, but instead diminish as dopamine neurons die. We observe a complete dissociation between apoptotic morphology and synuclein protein expression. We conclude that synuclein is unlikely to play a direct role in apoptotic death in dopamine neurons and is more likely, in the target injury model, to play a role in protection or restoration of neurons which survive.