ArticleNeurobiology of disease2015
Intrastriatal injection of pre-formed mouse α-synuclein fibrils into rats triggers α-synuclein pathology and bilateral nigrostriatal degeneration.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 1 of them a synthesis that pooled it.
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237 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- Preformed fibrils of α-synuclein rapidly activate LRRK2 on early endosomes, driving Rab5 phosphorylation and disrupting endolysosomal and synaptic function.NPJ Parkinson's disease · 2026Article
- Retinal Pathology and Synucleinopathy in the Visual Pathway of α-Synuclein Preformed Fibril Mouse Model of Parkinson's Disease.Brain and behavior · 2026Article
- Shared Epitope-PositiveNeurology(R) neuroimmunology & neuroinflammation · 2026Article
- Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.Journal of Parkinson's disease · 2026Article
- Microglia-T cell interactions drive α-synuclein pathology in a Parkinson's disease mouse model.Journal of neuroinflammation · 2026Article
- Antiviral innate immunity induces alpha synuclein phosphorylation at serine129 in neurons independent of aggregation.NPJ Parkinson's disease · 2026Article
- Testing an inverse link between limbic alpha-synucleinopathy and myelin markers in mice and humans.NPJ Parkinson's disease · 2026Article
- The Molecular Architecture of Neurodegeneration: An Integrative Overview of Convergent Mechanisms.NeuroSci · 2026Review
- Type I Interferons Drive the Gastrointestinal Inflammatory Response in a Mouse Model of Parkinson's Disease.Gastro hep advances · 2026Article
- Alpha-synuclein amyloids catalyze the degradation of ATP and other nucleotides.Scientific reports · 2025Article
- Lack of functional STING modulates immunity but does not protect dopaminergic neurons in the alpha-synuclein pre-formed fibrils Parkinson's disease mouse model.NPJ Parkinson's disease · 2025Article
- Attenuating α-synuclein pathology in mice with in situ engineered astrocytes.Translational neurodegeneration · 2025Article
- Article
- ATP Hydrolysis by α-Synuclein Amyloids is Mediated by Enclosing β-Strand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Alpha-synuclein overexpression does not cause vocalization deficits in a mouse model of parkinsonism.Biology open · 2025Article
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
- In silico identification of substrate-binding sites in type-1A α-synuclein amyloids.Biophysical journal · 2025Article
177 more citing papers are in PubMed but not listed here.
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Abstract
Previous studies demonstrate that intrastriatal injections of fibrillar alpha-synuclein (α-syn) into mice induce Parkinson's disease (PD)-like Lewy body (LB) pathology formed by aggregated α-syn in anatomically interconnected regions and significant nigrostriatal degeneration. The aim of the current study was to evaluate whether exogenous mouse α-syn pre-formed fibrils (PFF) injected into the striatum of rats would result in accumulation of LB-like intracellular inclusions and nigrostriatal degeneration. Sprague-Dawley rats received unilateral intrastriatal injections of either non-fibrillized recombinant α-syn or PFF mouse α-syn in 1- or 2- sites and were euthanized at 30, 60 or 180 days post-injection (pi). Both non-fibrillized recombinant α-syn and PFF α-syn injections resulted in phosphorylated α-syn intraneuronal accumulations (i.e., diffuse Lewy neurite (LN)- and LB-like inclusions) with significantly greater accumulations following PFF injection. LB-like inclusions were observed in several areas that innervate the striatum, most prominently the frontal and insular cortices, the amygdala, and the substantia nigra pars compacta (SNpc). α-Syn accumulations co-localized with ubiquitin, p62, and were thioflavin-S-positive and proteinase-k resistant, suggesting that PFF-induced pathology exhibits properties similar to human LBs. Although α-syn inclusions within the SNpc remained ipsilateral to striatal injection, we observed bilateral reductions in nigral dopamine neurons at the 180-day time-point in both the 1- and 2-site PFF injection paradigms. PFF injected rats exhibited bilateral reductions in striatal dopaminergic innervation at 60 and 180 days and bilateral decreases in homovanillic acid; however, dopamine reduction was observed only in the striatum ipsilateral to PFF injection. Although the level of dopamine asymmetry in PFF injected rats at 180 days was insufficient to elicit motor deficits in amphetamine-induced rotations or forelimb use in the cylinder task, significant disruption of ultrasonic vocalizations was observed. Taken together, our findings demonstrate that α-syn PFF are sufficient to seed the pathological conversion and propagation of endogenous α-syn to induce a progressive, neurodegenerative model of α-synucleinopathy in rats.
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