Disorders of the Nervous System
Author: Agostina Stahl | Email: astahl@fmed.uba.ar
Agostina Stahl1°, Analía López Díaz1°, Lorena Rela1°, Gustavo Murer1°
1° Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), UBA-CONICET
Parkinson’s disease (PD) motor symptoms emerge after striatal dopaminergic denervation and are associated with an imbalance between direct and indirect striatal projection pathways. These pathways are modulated by a diversity of striatal interneurons, some of which are relevant for the pathophysiology of motor symptoms in animal models of PD, as well as in models of abnormal movements (dyskinesias) that arise after dopamine replacement treatment with L-dopa, the gold standard therapy. Previous data indicate that striatal interneurons that co-express somatostatin, NPY, nitric oxide and GABA (iSOM+) have an altered activity in dyskinetic mice, but no study has yet addressed whether interventions on iSOM modify PD-like phenotypes or L-DOPA-induced dyskinesia (LID). We selectively eliminated iSOM+ via striatal diphtheria toxin administration in parkinsonian mice expressing the human diphtheria toxin receptor in iSOM (SOM-Cre;LSL-DTR mice). LSL-DTR mice treated with diphtheria toxin served as a control group. We use behavioral tests to evaluate the impact of iSOM+ ablation on the development and severity of LID in parkinsonian mice treated with increasing doses of L-dopa over 3 weeks. We expect to validate a model of striatal iSOM loss with potential applications to understand a variety of basal ganglia dysfunctions beyond PD and LID. Preliminary data will be presented at the meeting.