Parkinson's disease (PD) characterizes by a degeneration of mesencephalic dopaminergic neurons that innervate the striatum, a key nucleus for the selection of motor programs. In advanced stages of the disease only L-DOPA as a dopamine-replacement strategy

BECCARIA JP.; MARTOS Y.; MURER MG; BELFORTE JE

Cordoba

Congreso; Reunion Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2018

Sociedad Argentina de Investigación en Neurociencias (SAN)

Parkinson's disease (PD) characterizes by a degeneration of mesencephalic dopaminergic neuronsthat innervate the striatum, a key nucleus for the selection of motor programs. In advanced stagesof the disease only L-DOPA as a dopamine-replacement strategy allows an adequate performancein daily activities. However, the effectiveness of L-DOPA decreases and abnormal movementsemerge (dyskinesia). Striatal cholinergic interneurons (SCIN) are key modulators of striatal circuitsand are hyperexcitable in animal models of PD, owing to dysfunction of voltage-dependentpotassium channels containing Kv1.3 and Kv1.1 subunits which is not due to a decrease in Kv1.3protein expression. Enhanced SCIN activity was also linked to L-DOPA-induced dyskinesia (LID).Here we address whether SCIN dysfunction in mouse models of PD (unilateral lesion of the medialforebrain bundle with 6-OHDA) and LID is associated with an impaired trafficking of Kv1 channelsubunits to the plasma membrane. We use genetically modified mice that express a fluorescentmembrane marker (channelrhodopsin-EYFP fusion protein) in SCIN (ChAT-Cre;LSL-ChR2-EYFP) andanalyze the distribution of the Kv1.3 and Kv1.1 subunits in the plasma membrane and intracellularcompartments of SCIN, using immunohistochemistry. Preliminary results show that the fraction ofKv1.3 and Kv1.1 immunolabeling localized to the plasma membrane of SCIN in parkinsonian anddyskinetic mice did not differ from what was observed in unlesioned mice.