DEVELOPING A PRECLINICAL MODEL TO INVESTIGATE THE MOLECULAR BASIS OF DEPRESSION IN PD: IDENTIFICATION OF TRANSLATIONAL BIOMARKERS FOR CLINICAL APPLICATIONS

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder classically defined by motor symptoms, but increasingly recognized for its prominent non-motor manifestations, particularly depression. Depressive symptoms frequently precede motor impairment and are considered a potential early indicator of PD. Despite this, depression under PD context remains underdiagnosed and its contribution to disease progression, therapeutic response, and clinical outcomes is still poorly understood. Moreover, treatment is challenged by heterogeneous responses to antidepressants and their interactions with dopaminergic therapies. We aim to investigate the mechanisms linking depression and PD and to clarify how depressive-like states influence PD progression and treatment strategies. To address this, a novel pre-clinical model integrating PD-related pathology with depression-like features was developed, with preliminary data showing clear anhedonic-like behavior. The study combines behavioral assessments with neuropathological characterization and advanced imaging approaches, including ex vivo magnetic resonance imaging, to enable a comprehensive evaluation of structural and functional alterations associated with this comorbidity. By integrating behavioral, imaging, and pathological readouts, this project seeks to identify translational biomarkers and provide a robust platform to evaluate combined therapeutic strategies targeting both motor and non-motor symptoms in PD.