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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},
}