NDLI: Striatal dysregulation of Cdk5 alters locomotor responses to cocaine, motor learning, and dendritic morphology

Content Provider	PubMed Central
Author	Meyer, Douglas A. Richer, Edmond Benkovic, Stanley A. Hayashi, Kanehiro Kansy, Janice W. Hale, Carly F. Moy, Lily Y. Kim, Yong O'callaghan, James P. Tsai, Li-huei Greengard, Paul Nairn, Angus C. Cowan, Christopher W. Miller, Diane B. Antich, Pietro Bibb, James A.
Abstract	Motor learning and neuro-adaptations to drugs of abuse rely upon neuronal signaling in the striatum. Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine neurotransmission and behavioral responses to cocaine. Although the role for Cdk5 in neurodegeneration in the cortex and hippocampus and in hippocampal-dependent learning has been demonstrated, its dysregulation in the striatum has not been examined. Here we show that strong activation of striatal NMDA receptors produced p25, the truncated form of the Cdk5 co-activator p35. Furthermore, inducible overexpression of p25 in the striatum prevented locomotor sensitization to cocaine and attenuated motor coordination and learning. This corresponded with reduced dendritic spine density, increased neuro-inflammation, altered dopamine signaling, and shifted Cdk5 specificity with regard to physiological and aberrant substrates, but no apparent loss of striatal neurons. Thus, dysregulation of Cdk5 dramatically affects striatal-dependent brain function and may be relevant to non-neurodegenerative disorders involving dopamine neurotransmission.
Related Links	http://dx.doi.org/10.1073/pnas.0806078105
Ending Page	18566
Page Count	6
Starting Page	18561
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	47
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-11-25
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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