Home > Publications Database > Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease. > print

001     281109
005     20250924102922.0
024 7 _ |a 10.1177/0271678X251338952
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024 7 _ |a 0271-678X
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024 7 _ |a 1559-7016
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037 _ _ |a DZNE-2025-01070
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Lungu, Ruxanda
|b 0
245 _ _ |a Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease.
260 _ _ |a London
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520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a ASL
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650 _ 7 |a Parkinson’s disease
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650 _ 7 |a c-FOS
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650 _ 7 |a fMRI
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650 _ 7 |a α-Synuclein
|2 Other
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a SNCA protein, human
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins c-fos
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a alpha-Synuclein: genetics
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Parkinson Disease: physiopathology
|2 MeSH
650 _ 2 |a Parkinson Disease: genetics
|2 MeSH
650 _ 2 |a Parkinson Disease: complications
|2 MeSH
650 _ 2 |a Parkinson Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Cerebrovascular Circulation
|2 MeSH
650 _ 2 |a Olfactory Pathways: physiopathology
|2 MeSH
650 _ 2 |a Visual Pathways: physiopathology
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins c-fos: metabolism
|2 MeSH
650 _ 2 |a Brain: blood supply
|2 MeSH
700 1 _ |a Fernandes, Francisca F
|0 0000-0001-7967-067X
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700 1 _ |a Pires Monteiro, Sara
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700 1 _ |a Outeiro, Tiago F
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700 1 _ |a Shemesh, Noam
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773 _ _ |a 10.1177/0271678X251338952
|g Vol. 45, no. 9, p. 1654 - 1669
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|t Journal of cerebral blood flow & metabolism
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856 4 _ |u https://pub.dzne.de/record/281109/files/DZNE-2025-01070%20SUP.zip
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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