Banca de DEFESA: Rayanne Poletti Guimarães

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Rayanne Poletti Guimarães
DATE: 26/06/2025
TIME: 14:00
LOCAL: Plataforma Zoom
TITLE:

Development and characterization of experimental etiological models of Parkinson's disease in rodents

KEY WORDS:

Parkinson’s Disease, animal models, rodents, α-synuclein, 6- OHDA, viral vectors.

PAGES: 30
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and the presence of α-synuclein-containing inclusions, along with both motor and non-motor symptoms. Animal models are essential tools for understanding the underlying pathological processes, enabling the study of neurodegeneration mechanisms and the evaluation of therapeutic strategies in a controlled and translational manner. This thesis aimed to optimize and characterize experimental models of PD in rodents, focusing in Chapter 1 on the combination of αsynuclein aggregates and dopaminergic lesion, and in Chapter 2 on the effects of human α-synuclein in cholinergic pathways associated with non-motor symptoms. In Chapter 1, a combined model was developed in mice using intrastriatal infusion of preformed fibrils (PFFs) of α-synuclein, followed by 6-hydroxydopamine (6-OHDA). This model induced the formation of pathological inclusions and dopaminergic loss (construct validity), led to progressive motor deficits (face validity), and responded to L-DOPA treatment (predictive validity). These findings support the translational relevance of the combined model, which recapitulates key features of PD. In Chapter 2, an independent model was developed in rats using AAV-mediated expression of human α-synuclein in the prefrontal cortex (PFC) and the nucleus basalis of Meynert (nbM). Robust expression of the protein was observed in the target regions, along with the presence of phosphorylated α-synuclein (pSer129) and colocalization with cholinergic neurons, indicating pathological protein generation and internalization by these neurons. These results provide a basis for studying the early mechanisms of cholinergic dysfunction in PD-related non-motor symptoms. Both models contribute complementary approaches to the study of PD, addressing distinct motor and non-motor aspects, and expanding the repertoire of translational tools for future therapeutic strategies.

COMMITTEE MEMBERS:
Externa à Instituição - IVANI BRYS - UFSM
Externa à Instituição - ALESSANDRA MUSSI RIBEIRO - UNIFESP
Externa ao Programa - 1302038 - LUANA CRISTINA CAMARGO - nullInterna - 2567703 - MARCIA RENATA MORTARI
Externo ao Programa - 1952915 - RAFAEL PLAKOUDI SOUTO MAIOR - null