CDK5 Modulates Morphological Plasticity of Dendritic Spines Induced by Amphetamines in Hippocampal Pyramidal Neurons

FERRERAS S., PISANO V., KRAPACHER F., POZZO MILLER L., PAGLINI M.G.

Huerta Grande, Córdoba, Argentina

Congreso; IRCN, First Joint Meeting of the Argentine Society for Neurosciences (SAN) and the Argentine Workshop in Neurosciences (TAN); 2009

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

Experience-dependent changes in behavior are thought to involve structural modifications in the central nervous systems, especially alterations in patterns of synaptic connectivity. However, little is known about the morphological plasticity occurring during exposure to drugs of abuse. One of the targets of structural plasticity are the dendritic spines, which are dynamics, actin-rich protrusions. Recent reports have suggested that cdk5 plays an important role in drug addiction. In this study, we tested the role of cdk5 in amphetamine (Amph)-induced dendritic spines formation. Hippocampal slices maintained in organotypic tissue culture were biolistically-transfected with cDNAs coding for eYFP and exposed to different doses of Amph (50 and 100uM) for 48h. Quantitative analyses of dendritic spines density and morphological spines type. Interestingly, cdk5 inhibition by expression of a dominant negative mutant during Amph exposure, decreased spine density. These results suggest that Amph-Induced spine formation require intact cdk5 activity and encourage us to propose cdk5/p35 an a excellent candidate that might mediate the regulation of actin cytoskeleton, trough the phosphoryation of specific substrate to test in future experiments, since is in a key protein that switch from active to inactive state and thereby mediate the rapid dynamic regulation of the actin cytoskeleton, essential in dendritic spine morphogenesis,