Increased expression of cyclin-dependent kinase 5 in induced apoptotic neuron death in rat substantia nigra.
We reported previously that striatal excitotoxic lesion with quinolinic acid of rat pups during the first 2 weeks of postnatal life results in loss of dopaminergic neurons of the substantia nigra (SN) due to induced apoptosis. Here we demonstrate by immunohistochemistry that, following such a lesion, high levels of cyclin-dependent kinase 5 (cdk5) protein are present exclusively in apoptotic cells over and above basal levels of diffuse axonal staining. Furthermore, localization of high levels of cdk5 is associated also with normal developmental programmed cell death in the SN and other regions of the central nervous system, including the cerebral cortex. These findings suggest a novel role for cdk5 during neuron apoptosis and may provide insight into mechanisms of loss of dopaminergic neurons in Parkinson's disease.
Henchcliffe
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Department of Neurology, Columbia University, New York, NY 10032, USA.
Burke
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D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D004790:Enzyme Induction; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009498:Neurotoxins; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors
D009498:Neurotoxins; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D017378:Quinolinic Acid