ArticleBrain pathology (Zurich, Switzerland)2022
Impact of α-synuclein spreading on the nigrostriatal dopaminergic pathway depends on the onset of the pathology.
Article in Brain pathology (Zurich, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 19 citations in OpenAlex.
- Inhibition of Abnormal Elevated α-Synuclein Ameliorates Dopaminergic Neuron Degeneration in Parkinson's Disease Mouse Model.Aging cell · 2026Article
- Vascular Risk Factors and the Risk of Incident Parkinson's Disease Among Stroke Survivors: A Nationwide Population-Based Cohort Study.Journal of clinical medicine · 2026Article
- α-Synuclein oligomers slow down action potential firing and enhance dopamine release by increasing Cav2.2 currents in midbrain dopaminergic neurons.The Journal of physiology · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
- Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.Journal of Parkinson's disease · 2024Article
- Developmental exposure to the Parkinson's disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Impaired dopamine release in Parkinson's disease.Brain : a journal of neurology · 2023Review
- Alpha-synuclein pre-formed fibrils injected into prefrontal cortex primarily spread to cortical and subcortical structures and lead to isolated behavioral symptoms.bioRxiv : the preprint server for biology · 2023Article
- Aging exacerbates the brain inflammatory micro-environment contributing to α-synuclein pathology and functional deficits in a mouse model of DLB/PD.Molecular neurodegeneration · 2022Article
- Impact of α-synuclein spreading on the nigrostriatal dopaminergic pathway depends on the onset of the pathology.Brain pathology (Zurich, Switzerland) · 2022Article
- Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson's Disease Pathogenesis: A Narrative Review.Brain sciences · 2022Review
- Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson's Disease.Frontiers in aging neuroscience · 2022Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Misfolded α-synuclein spreads along anatomically connected areas through the brain, prompting progressive neurodegeneration of the nigrostriatal pathway in Parkinson's disease. To investigate the impact of early stage seeding and spreading of misfolded α-synuclein along with the nigrostriatal pathway, we studied the pathophysiologic effect induced by a single acute α-synuclein preformed fibrils (PFFs) inoculation into the midbrain. Further, to model the progressive vulnerability that characterizes the dopamine (DA) neuron life span, we used two cohorts of mice with different ages: 2-month-old (young) and 5-month-old (adult) mice. Two months after α-synuclein PFFs injection, we found that striatal DA release decreased exclusively in adult mice. Adult DA neurons showed an increased level of pathology spreading along with the nigrostriatal pathway accompanied with a lower volume of α-synuclein deposition in the midbrain, impaired neurotransmission, rigid DA terminal composition, and less microglial reactivity compared with young neurons. Notably, preserved DA release and increased microglial coverage in the PFFs-seeded hemisphere coexist with decreased large-sized terminal density in young DA neurons. This suggests the presence of a targeted pruning mechanism that limits the detrimental effect of α-synuclein early spreading. This study suggests that the impact of the pathophysiology caused by misfolded α-synuclein spreading along the nigrostriatal pathway depends on the age of the DA network, reducing striatal DA release specifically in adult mice.
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