Neurodevelopmental-Immune Continuum Hypothesis for Parkinson’s disease

Objetivo temático: This study aims to establish a continuum framework linking prenatal immune disturbances to age-specific brain disorder onset, providing critical insights into potential early interventions and prevention strategies for these interrelated conditions.

Área Científica: Good Health and Well-being

Síntese do Projeto: Emerging evidence suggests that Parkinson disease (PD) is tied to immune dysregulation. This project hypothesizes a continuum model, where prenatal immune disruption, including maternal immune activation (MIA), and subsequent postnatal immune challenges predisposes individuals to PD. MIA, triggered by prenatal infections, significantly impacts fetal immune development by altering both brain and gut immunity. This immune dysregulation begins in utero, as fetal immune cells are exposed to maternal cytokines and microbiota-derived metabolites, influencing brain development and priming the immune system for enhanced inflammatory responses. Disruptions to microglial migration, as well as the alteration in the establishment of gut-associated immunity, increase susceptibility to further immune challenges encountered postnatally, which can influence the timing and type of disorder manifestation. We propose that these neuroimmune changes and late-life chronic inflammation may trigger PD pathology. By using a “two-hit” mouse model of MIA, we will investigate how prenatal immune activation, and postnatal inflammatory exposures interact to shape neurodevelopmental and neurodegenerative outcomes.

Investigador Responsável na UC: Sandra Morais Cardoso (PI) e Raquel Pereira Santos (PhD student)

Unidade Orgânica UC: Reitoria - CNC

Instituições participantes no Projeto: Universidade de Coimbra

Instituição Financiadora/Gestora: Parkinson’s and Movement Disorder Foundation (PMDF)

Programa de Financiamento: PMDF - Movement Disorder Grant 2024

Período de execução: 01.03.2025 - 28.02.2026

Custo total elegível (EUR): 5 000,00 $

Técnico do Projeto: Kayleigh Mikaela Oliveira Rodrigues

Contacto: 239 247 016 | kayleigh.rodrigues@uc.pt