INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cdk5/p25 Complex Modulates Morphological Plasticity of Dendritic Spines Induced by Amphetamine
Autor/es:
FERRERAS SOLEDAD; PISANO MARÍA VICTORIA; FERNÁNDEZ GUILLERMO; POZZO-MILLER LUCAS; PAGLINI GABRIELA
Reunión:
Congreso; XXVIII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2013
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS
Resumen:
Cdk5 is a serine/threonine kinase that is activated by association with a regulatory subunit p35. The cdk5/p35 complex has been involved in several fundamental processes during normal brain development, including neuronal migration, axonal and dendritic formation, synaptic plasticity, as well as in associative learning and memory (Dhavan R and Tsai LH, 2001.Nat Rev Mol Cell Biol. 2(10):749-59; Fischer A, et al., 2005 Neuron 48(5):825-38). Several reports have suggested that cdk5 plays an important role in addiction to drugs of abuse (Benavides DR and Bibb JA, 2004 Ann NY Acad Sci 1025:335-44; Mlewski EC, et al., 2008 Ann NY Acad Sci 1139:89-102). It is well known that psychostimulant drugs alter synaptic transmission in the reward centers of the brain, and that synaptic plasticity mechanisms in those regions are targets of drugs of abuse (Hyman SE and Malenka RC, 2001 Nat Rev Neurosci 2(10):695-703; Nestler EJ, 2001 J Neurosci 21(21):8324-7). Notably, exposure to cocaine or amphetamine increases the number of dendritic branches and dendritic spines in reward system areas of the brain, suggesting that underlies enduring synaptic plasticity alterations (Li Y, et al., 2003 Neuropsychopharmacology 28(6):1082-5; Robinson TE and Kolb B, 2004 Neuropharmacology 47 Suppl 1:33-46). However, little is known about the molecular mechanisms that regulate these effects. Previous results from our lab demonstrated that 48hr exposure to Amphetamine 50uM (Amph) increased dendritic spine density in hippocampal slice cultures. Moreover, Cdk5 inhibition by expression of a dominant negative Cdk5 mutant (DN-Cdk5) prevented the increase on dendritic spine density. The aim of the present study was to further test Cdk5 participation in Amph-induced dendrittic spine generation and to determinate the role Cdk5 activators (p35 and p25) play in this phenomenon.