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@ARTICLE{Lungu:281109,
author = {Lungu, Ruxanda and Fernandes, Francisca F and Pires
Monteiro, Sara and Outeiro, Tiago F and Shemesh, Noam},
title = {{N}eural and vascular contributions to sensory impairments
in a human alpha-synuclein transgenic mouse model of
{P}arkinson's disease.},
journal = {Journal of cerebral blood flow $\&$ metabolism},
volume = {45},
number = {9},
issn = {0271-678X},
address = {London},
publisher = {Sage},
reportid = {DZNE-2025-01070},
pages = {1654 - 1669},
year = {2025},
abstract = {Parkinson's disease (PD) is a complex progressive
neurodegenerative disorder involving hallmarks such as
α-Synuclein (αSyn) 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 αSyn 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 αSyn
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 αSyn-based model,
and suggests a novel target for biomarking via
quantification of simple sensory evoked responses.},
keywords = {Animals / Mice, Transgenic / alpha-Synuclein: genetics /
alpha-Synuclein: metabolism / Humans / Mice / Magnetic
Resonance Imaging / Parkinson Disease: physiopathology /
Parkinson Disease: genetics / Parkinson Disease:
complications / Parkinson Disease: diagnostic imaging /
Disease Models, Animal / Male / Cerebrovascular Circulation
/ Olfactory Pathways: physiopathology / Visual Pathways:
physiopathology / Proto-Oncogene Proteins c-fos: metabolism
/ Brain: blood supply / ASL (Other) / Parkinson’s disease
(Other) / c-FOS (Other) / fMRI (Other) / α-Synuclein
(Other) / alpha-Synuclein (NLM Chemicals) / SNCA protein,
human (NLM Chemicals) / Proto-Oncogene Proteins c-fos (NLM
Chemicals)},
cin = {AG Fischer},
ddc = {610},
cid = {I:(DE-2719)1410002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40334688},
pmc = {pmc:PMC12058711},
doi = {10.1177/0271678X251338952},
url = {https://pub.dzne.de/record/281109},
}