Striatal structural plasticity beyond dopamine agonist-induced abnormal involuntary movements

TRIBBIA LT.; BELFORTE JE.; MURER MG.; GERSHANIK OS.; TARAVINI IRE.

Buenos Aires

Congreso; XXXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2022

Sociedad Argentina de Investigación en Neurociencia

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide. L-DOPA administration is currently the most effective symptomatic drug therapy, but long-term treatment leads to the development of L-DOPA-induced dyskinesia (LID). There is consensus that striatal neurons undergo changes in their dendritic and synaptic microarchitecture associated with LID. However, there is little information on the occurrence of changes in striatal microarchitecture in animals that develop abnormal involuntary movements (AIM) due to chronic treatment with selective D1 or D2 agonists. We propose to determine if striatal neurons undergo structural plastic changes after the development of AIMs by chronic treatment with selective dopamine agonists in an animal model of PD. C57BL/6J mice lesioned with a unilateral injection of 6-OHDA or vehicle in the mfb were treated with SKF-38393 D1R agonist (2mg/kg), QUINPIROLE D2R agonist (QP) (0.5mg/kg) or distilled water for 15 days. Axial, limb and orofacial AIMs were measured after each administration, using a validated rating scale.The fixed brain tissue is being processed to analyze the striatal synaptic structure. AIMs analysis showed that lesioned mice treated with QP developed more severe axial AIMs, while mice treated with SKF exhibited orofacial AIMs mainly.Analysis of the density of dendritic spines will allow correlating the occurrence of structural changes in the synapses of striatal neurons with the development of AIMs.