Neuroinflammatory Mechanisms and Vocalization Biomarkers in the Pink1-/- Preclinical Model of Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder with an unclear etiology and a long preclinical phase. The multitude of challenges of studying this in humans highlight the need for robust preclinical animal models that accurately reflect the disease's preclinical progression. While traditional neurotoxin models fail to capture the slow, genetic nature of PD, genetic models, such as the phosphatase and tensin homolog-induced putative kinase 1 (<i>Pink1</i>-/-) knockout rat, offer a preclinical, translational approach. This review synthesizes the current understanding of the <i>Pink1</i>-/- rat model, focusing on two key aspects: neuroinflammation and vocalization deficits. The <i>Pink1</i>-/- rat presents early non-motor symptoms, including vocalization deficits, which can serve as a non-invasive, objective, and longitudinal biomarker of disease progression. This review further proposes a direct link between the model's neuroinflammatory profile, characterized by chronic glial activation and the upregulation of inflammatory pathways, and the observed vocal dysfunctions. By bridging these two critical areas, neuroinflammation as a pathological mechanism and vocalizations as a functional readout, this review provides a framework for future investigations into the diagnosis and treatment of Parkinson's disease and suggests that targeting specific inflammatory pathways could be a viable therapeutic strategy.