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000281109 041__ $$aEnglish
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000281109 1001_ $$aLungu, Ruxanda$$b0
000281109 245__ $$aNeural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson's disease.
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000281109 520__ $$aParkinson's disease (PD) is a complex progressive neurodegenerative disorder involving hallmarks such as α-Synuclein (αSyn) aggregation and dopaminergic dysfunction that affect brain-wide neural activity. Although movement disorders are prominent in PD, sensory impairments also occur relatively early on, mainly in olfactory and, to a lesser extent visual systems. While these deficits have been described mainly at the behavioral and molecular levels, the underlying network-level activity remains poorly understood. Here, we harnessed a human αSyn transgenic mouse model of PD with in vivo functional MRI (fMRI) to map evoked activity in the visual and olfactory pathways, along with pseudo-Continuous Arterial Spin Labeling (pCASL) and c-FOS measurements to disentangle vascular from neuronal effects. Upon stimulation with either odors or flickering lights, we found significant decreases in fMRI responses along both olfactory and visual pathways, in multiple cortical and subcortical sensory areas. Average Cerebral Blood Flow rates were decreased by ∼10% in the αSyn group, while c-FOS levels were reduced by over 50%, suggesting a strong neural driver for the dysfunction, along with more modest vascular contributions. Our study provides insight into brain-level activity in an αSyn-based model, and suggests a novel target for biomarking via quantification of simple sensory evoked responses.
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000281109 650_7 $$2Other$$aASL
000281109 650_7 $$2Other$$aParkinson’s disease
000281109 650_7 $$2Other$$ac-FOS
000281109 650_7 $$2Other$$afMRI
000281109 650_7 $$2Other$$aα-Synuclein
000281109 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000281109 650_7 $$2NLM Chemicals$$aSNCA protein, human
000281109 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-fos
000281109 650_2 $$2MeSH$$aAnimals
000281109 650_2 $$2MeSH$$aMice, Transgenic
000281109 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000281109 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000281109 650_2 $$2MeSH$$aHumans
000281109 650_2 $$2MeSH$$aMice
000281109 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000281109 650_2 $$2MeSH$$aParkinson Disease: physiopathology
000281109 650_2 $$2MeSH$$aParkinson Disease: genetics
000281109 650_2 $$2MeSH$$aParkinson Disease: complications
000281109 650_2 $$2MeSH$$aParkinson Disease: diagnostic imaging
000281109 650_2 $$2MeSH$$aDisease Models, Animal
000281109 650_2 $$2MeSH$$aMale
000281109 650_2 $$2MeSH$$aCerebrovascular Circulation
000281109 650_2 $$2MeSH$$aOlfactory Pathways: physiopathology
000281109 650_2 $$2MeSH$$aVisual Pathways: physiopathology
000281109 650_2 $$2MeSH$$aProto-Oncogene Proteins c-fos: metabolism
000281109 650_2 $$2MeSH$$aBrain: blood supply
000281109 7001_ $$00000-0001-7967-067X$$aFernandes, Francisca F$$b1
000281109 7001_ $$aPires Monteiro, Sara$$b2
000281109 7001_ $$0P:(DE-2719)2814138$$aOuteiro, Tiago F$$b3$$udzne
000281109 7001_ $$00000-0001-6681-5876$$aShemesh, Noam$$b4
000281109 773__ $$0PERI:(DE-600)2039456-1$$a10.1177/0271678X251338952$$gVol. 45, no. 9, p. 1654 - 1669$$n9$$p1654 - 1669$$tJournal of cerebral blood flow & metabolism$$v45$$x0271-678X$$y2025
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