"Selective vulnerability in dopaminergic neurons in Parkinson’s Disease"

Parkinson's Disease (PD) is characterized by the selective degeneration of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), while neurons in the Ventral Tegmental Area (VTA) exhibit greater resilience. Understanding the molecular basis of this differential vulnerability is essential to identify the onset of the pathology during the prodromal phase, when dopaminergic neurons have not yet undergone cell death but already present functional alterations. Identifying early signals at this stage is crucial for the development of effective neuroprotective strategies. The objective of this thesis is to analyze the expression of specific markers, such as Tyrosine Hydroxylase (TH), Calbindin (CB), and ALDH1A1, in the SNc and VTA, using the Ndufs2 mitochondrial subunit I conditional knockout mouse model, which mimics the neurodegenerative state characteristic of Parkinson's Disease (PD). Through immunofluorescence and fluorescence microscopy, a spatial mapping was conducted to localize these markers and compare their expression levels in wild-type (WT) and pathological conditions (KO). This investigation aims to determine whether the expression of these biomarkers is correlated with selective neuronal vulnerability and the progressive loss of dopaminergic neurons or if their presence may confer an intrinsic neuroprotective advantage to resilient dopaminergic subpopulations.