ArticleBrain : a journal of neurology2021
Dopamine-dependent early synaptic and motor dysfunctions induced by α-synuclein in the nigrostriatal circuit.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 117 citations in OpenAlex.
- Chronic Paraquat Neurotoxicity and Dopaminergic Degeneration: A Mechanistic Review.Chemistry & biodiversity · 2026Review
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- α-Synuclein pathology differentially alters T-type calcium currents in vulnerable and resilient substantia nigra dopaminergic subpopulations.bioRxiv : the preprint server for biology · 2026Article
- Targeting GPCR Signaling in Parkinson's Disease: From Molecular Pathology to Exercise-Based Therapeutics.Molecular neurobiology · 2026Review
- Age-related susceptibility to paraquat-induced neurotoxicity in male wistar rats: effects on neurobehaviour, substantia nigra cytoarchitecture, and alpha-synuclein levels.BMC neuroscience · 2026Article
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Role of Netrin-1 dysregulation in early neuronal pathology of α-synuclein models of Parkinson's disease.Journal of advanced research · 2026Article
- Dopamine-endocannabinoid crosstalk drives exercise-induced bidirectional plasticity in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Molecular Pathogenesis of Memory Impairment in Parkinson's Disease: An Exploration of Underlying Mechanisms.Health science reports · 2026Article
- Investigation of the In Vitro Neuroprotective Potential of Aegiceras corniculatum against MPTP-induced Toxicity.Applied biochemistry and biotechnology · 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
- Relationship between frailty and disease progression in Parkinson's disease: a 3-year longitudinal study.GeroScience · 2026Article
- Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.Translational neurodegeneration · 2026Article
- Alpha-synuclein overexpression reduces neural activity within a basal ganglia vocal nucleus in a zebra finch model.PloS one · 2026Article
- The North American Prodromal Synucleinopathy study: protocol for a multi-site, longitudinal, observational study of idiopathic/isolated rapid eye movement sleep behavior disorder.Sleep advances : a journal of the Sleep Research Society · 2026Article
- Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Backtracking α-synuclein pathology: social deficits precede motor symptoms in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Review
12 more citing papers are in PubMed but not listed here.
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18 authors at 9 institutions in 1 country.
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Abstract
Misfolding and aggregation of α-synuclein are specific features of Parkinson's disease and other neurodegenerative diseases defined as synucleinopathies. Parkinson's disease progression has been correlated with the formation and extracellular release of α-synuclein aggregates, as well as with their spread from neuron to neuron. Therapeutic interventions in the initial stages of Parkinson's disease require a clear understanding of the mechanisms by which α-synuclein disrupts the physiological synaptic and plastic activity of the basal ganglia. For this reason, we identified two early time points to clarify how the intrastriatal injection of α-synuclein-preformed fibrils in rodents via retrograde transmission induces time-dependent electrophysiological and behavioural alterations. We found that intrastriatal α-synuclein-preformed fibrils perturb the firing rate of dopaminergic neurons in the substantia nigra pars compacta, while the discharge of putative GABAergic cells of the substantia nigra pars reticulata is unchanged. The α-synuclein-induced dysregulation of nigrostriatal function also impairs, in a time-dependent manner, the two main forms of striatal synaptic plasticity, long-term potentiation and long-term depression. We also observed an increased glutamatergic transmission measured as an augmented frequency of spontaneous excitatory synaptic currents. These changes in neuronal function in the substantia nigra pars compacta and striatum were observed before overt neuronal death occurred. In an additional set of experiments, we were able to rescue α-synuclein-induced alterations of motor function, striatal synaptic plasticity and increased spontaneous excitatory synaptic currents by subchronic treatment with l-DOPA, a precursor of dopamine widely used in the therapy of Parkinson's disease, clearly demonstrating that a dysfunctional dopamine system plays a critical role in the early phases of the disease.
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