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

GUILLERMO FERNÁNDEZ; ANTONELLA MONTEMERLO; MARIA DOLORES RUBIANES; GABRIELA PAGLINI

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Abnormal dopaminergic system functioning has been related to a broad of psychiatry disorders such as Parkinson, Schizophrenia, Attention Deficit Hyperactivity Disorder, among others. One of the key proteins regulating Dopamine (DA) strength 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, due to 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 mice.Through biotinylation assays, we demonstrated that p35KO mice exhibit reduced DAT surface expression in striatal synaptosomes compared to WT control mice, although total DAT levels do not differ between genotypes. In agreement with these results, amperometric measurements of DA reuptake, using 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.