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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Parkinson's disease (PD) is a complex progressive neurodegenerative disorder involving hallmarks such as (Formula presented.) -Synuclein ((Formula presented.) Syn) aggregation and dopaminergic dysfunction that affect brain-wide neural activity. Although movement disorders are prominent in PD, sensory impairments also occur relatively early on, mainly in olfactory and, to a lesser extent visual systems. While these deficits have been described mainly at the behavioral and molecular levels, the underlying network-level activity remains poorly understood. Here, we harnessed a human (Formula presented.) Syn transgenic mouse model of PD with in vivo functional MRI (fMRI) to map evoked activity in the visual and olfactory pathways, along with pseudo-Continuous Arterial Spin Labeling (pCASL) and c-FOS measurements to disentangle vascular from neuronal effects. Upon stimulation with either odors or flickering lights, we found significant decreases in fMRI responses along both olfactory and visual pathways, in multiple cortical and subcortical sensory areas. Average Cerebral Blood Flow rates were decreased by ∼10% in the (Formula presented.) Syn group, while c-FOS levels were reduced by over 50%, suggesting a strong neural driver for the dysfunction, along with more modest vascular contributions. Our study provides insight into brain-level activity in an (Formula presented.) Syn-based model, and suggests a novel target for biomarking via quantification of simple sensory evoked responses.
Author(s): Lungu R, Fernandes FF, Pires Monteiro S, Outeiro TF, Shemesh N
Publication type: Article
Publication status: Published
Journal: Journal of Cerebral Blood Flow and Metabolism
Year: 2025
Volume: 45
Issue: 9
Pages: 1654-1669
Print publication date: 01/09/2025
Online publication date: 07/05/2025
Acceptance date: 14/04/2025
Date deposited: 19/05/2025
ISSN (print): 0271-678X
ISSN (electronic): 1559-7016
Publisher: Sage Publications Ltd.
URL: https://doi.org/10.1177/0271678X251338952
DOI: 10.1177/0271678X251338952
Data Access Statement: The authors confirm that the data supporting the findings of this study will be made available on a free repository. The code used to analyze the fMRI data analysis will be shared upon request.
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