Expression of cyclin-dependent kinase 5 and its activator p35 in models ofinduced apoptotic death in neurons of the substantia nigra in vivo

Cyclin-dependent kinase 5 is predominantly expressed in postmitotic neurons and plays a role in neurite elongation during development. It has also bee n postulated to play a role in apoptosis in a variety of cells, including n eurons, but little is known about the generality and functional significanc e of cdk5 expression in neuronal apoptosis in living brain. We have therefo re examined its expression and that of its known activators, p35, p39 and p 67, in models of induced apoptosis in neurons of the substantia nigra. We f ind that cdk5 is expressed in apoptotic profiles following intrastriatal in jection of 6-hydroxydopamine and axotomy. It is expressed exclusively in pr ofiles which are in late morphologic stages of apoptosis. In these late sta ges, derivation of the profiles from neurons, and localization of expressio n to the nucleus, can be demonstrated by co-labeling with a neuron-specific nuclear marker, NeuN. In another model of induced apoptotic death in nigra , produced by developmental striatal lesion, kinase activity increases in p arallel with cell death. While mRNAs for all three cdk5 activators are expr essed in nigra during development, only p35 protein is expressed in apoptot ic profiles. We conclude that cdk5/p35 expression is a general feature of a poptotic neuron death in substantia nigra neurons in vivo.