Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

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

Authors
Meyer-DA; Richer-E; Benkovic-SA; Hayashi-KJ; Kansy-JW; Hale-CF; Moy-LY; Kim-Y; O'Callaghan-JP; Tsai-LH; Greengard-P; Nairn-AC; Cowan-CW; Miller-DB; Antich-P; Bibb-JA
Source
Proc Natl Acad Sci U.S.A. 2008 Nov; 105(47):18561-18566
NIOSHTIC No.
20034774
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.
Keywords
Brain-function; Drug-receptor; Substance-abuse; Neurological-system; Neuromotor-system; Neurotransmitters; Nerve-fibers; Neurological-reactions; Neurophysiological-effects; Neurophysiology; Neurological-system; Neuromotor-system-disorders
Contact
James A. Bibb, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390
CODEN
PNASA6
Publication Date
20081125
Document Type
Journal Article
Email Address
james.bibbo@utsouthwestern.edu
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
47
ISSN
0027-8424
NIOSH Division
HELD
Priority Area
Services
Source Name
Proceedings of the National Academy of Sciences of the United States of America.
State
GA; TX; MA; NY; CT
TOP