Journal Article

DZNE-2025-01070

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease.

Lungu, R. ; Fernandes, F. F. ; Pires Monteiro, S. ; Outeiro, T. F.DZNE* ; Shemesh, N.

2025
Sage London

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Please use a persistent id in citations: doi:10.1177/0271678X251338952

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.

Keyword(s): Animals (MeSH) ; Mice, Transgenic (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Parkinson Disease: physiopathology (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: complications (MeSH) ; Parkinson Disease: diagnostic imaging (MeSH) ; Disease Models, Animal (MeSH) ; Male (MeSH) ; Cerebrovascular Circulation (MeSH) ; Olfactory Pathways: physiopathology (MeSH) ; Visual Pathways: physiopathology (MeSH) ; Proto-Oncogene Proteins c-fos: metabolism (MeSH) ; Brain: blood supply (MeSH) ; ASL ; Parkinson’s disease ; c-FOS ; fMRI ; α-Synuclein ; alpha-Synuclein ; SNCA protein, human ; Proto-Oncogene Proteins c-fos

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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