Evidence of the role of Cyclin Dependent Kinase 5 in DAT expression and functioning

GUILLERMO FERNÁNDEZ; MACARENA MARI; ANTONELLA MONTEMERLO; MARÍA DOLORES RUBIANES; MARÍA GABRIELA PAGLINI

Carlos Paz

Congreso; XXXIV Reunión Anual SAN 2019-Congreso de la Sociedad Argentina de Neurociencias; 2019

Sociedad Argentina de Neurociencias

Abnormal dopaminergic system functioning has been related to a broad of psychiatry disorders such as Parkinson, Schizophrenia, Attention Deficit Hyperactivity Disorder, amongothers. One of the key proteins that regulate Dopamine (DA) transmission efficiency is Cyclin dependent kinase 5 (Cdk5). In this sense, mice lacking Cdk5 activator, p35 (p35KO) mimic the symptoms and shared ADHD dopaminergic abnormalities. Thereby, p35KO mice display an increased DA striatal content, an augmented DA synthesis pathway and decreased DA metabolism. Given that, DA neurotransmission is modulated by Dopamine Transporter (DAT), which mediates the reuptake of DA, we studied DAT surface expression and uptake capacity in striatum of p35KO and WT control mice. Through biotinylation assays, we demonstrated that p35KO mice exhibit reduced DAT surface expression in striatal synaptosomes compared to WT mice, although total DAT levels do not differ betweengenotypes. In agreement with these results, amperometric measurements of DA reuptake, using a nanostructured electrochemical sensor based on a glassy carbon electrode modified with carbon nanotube as analytical platform, showed that p35KO mice present a decrease of DA uptake compared with WT animals. These results suggest a critical role of Cdk5 in DAT expression and functioning and provide new insights of the regulation of DA neurotransmission in neuropsychiatric disorders.