The expression of Cellular Prion Protein (PrPC) increases Parkinson's Disease neurodegeneration in mice

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and other regions of the extrapyramidal pathway, along with the presence of intraneuronal α-synuclein oligomers (αSO). Recent research suggests that the internalization of αSO may be facilitated by the native trafficking of Cellular Prion Protein (PrPC), a glycoprotein highly expressed in the Central Nervous System. This study aims to investigate the role of PrPC in an in vivo model of PD. Stereotaxic intrastriatal injections of 2μg αSO were administered to wild-type (WT) mice, PrPC knockout (PrPKO) mice, and mice overexpressing PrPC (TG20), aged 60 to 90 days (n=4). Subsequently, behavioral assessments including the Rotarod test, Wire Hanging test (WHT), Pole test, Olfactory Discrimination test (ODT), and Open Field test were conducted at 7- and 30-days post-injection. Statistical analysis was performed using two-way ANOVA. All procedures adhered to the guidelines set by the Animal Use Ethics Committee (CEUA) of the Health Sciences Center (CCS) of UFRJ, approved by protocol number A6/19-001-16. Results revealed a trend of reduced latency time to fall from the Rotarod, indicating motor function decline in WT and TG20 mice, but not in PrPKO mice. The WHT showed a trend of reduced time spent on the grid platform in TG20 mice, suggestive of gross motor impairment. Additionally, the ODT demonstrated a reduced ability to recognize compartments with familiar odor in TG20 mice treated with αSO, indicating olfactory acuity impairment. Immunohistochemistry assays with anti-Tyrosine hydroxylase (TH) antibody revealed a significant reduction in TH intensity in the caudate-putamen nucleus of the striatum in WT and TG20 mice injected with αSO, but not in PrPKO mice. These preliminary findings suggest a potential association between PrPC expression levels and the neurodegenerative process characteristic of PD.