TY  - JOUR
AU  - Lungu, Ruxanda
AU  - Fernandes, Francisca F
AU  - Pires Monteiro, Sara
AU  - Outeiro, Tiago F
AU  - Shemesh, Noam
TI  - Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease.
JO  - Journal of cerebral blood flow & metabolism
VL  - 45
IS  - 9
SN  - 0271-678X
CY  - London
PB  - Sage
M1  - DZNE-2025-01070
SP  - 1654 - 1669
PY  - 2025
AB  - 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
KW  - Animals
KW  - Mice, Transgenic
KW  - alpha-Synuclein: genetics
KW  - alpha-Synuclein: metabolism
KW  - Humans
KW  - Mice
KW  - Magnetic Resonance Imaging
KW  - Parkinson Disease: physiopathology
KW  - Parkinson Disease: genetics
KW  - Parkinson Disease: complications
KW  - Parkinson Disease: diagnostic imaging
KW  - Disease Models, Animal
KW  - Male
KW  - Cerebrovascular Circulation
KW  - Olfactory Pathways: physiopathology
KW  - Visual Pathways: physiopathology
KW  - Proto-Oncogene Proteins c-fos: metabolism
KW  - Brain: blood supply
KW  - ASL (Other)
KW  - Parkinson’s disease (Other)
KW  - c-FOS (Other)
KW  - fMRI (Other)
KW  - α-Synuclein (Other)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - SNCA protein, human (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-fos (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40334688
C2  - pmc:PMC12058711
DO  - DOI:10.1177/0271678X251338952
UR  - https://pub.dzne.de/record/281109
ER  -