ArticleScientific reports2020
Norepinephrine depleting toxin DSP-4 and LPS alter gut microbiota and induce neurotoxicity in α-synuclein mutant mice.
Article in Scientific reports, 2020. 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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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- From dysbiosis to dysfunction: specific gut microbes and metabolites in the pathogenesis of Parkinson's disease.Sustainable microbiology · 2026Review
- Microbiota-Gut-Brain Axis in Neurodegenerative Diseases: The Role of Bacterial Amyloids.Cellular and molecular gastroenterology and hepatology · 2026Review
- Microbiome-Gut-Brain Axis: Implications for the Links Between Inflammatory Bowel Disease and Neuropsychiatric Disorders.Journal of inflammation research · 2025Review
- Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.Therapeutic advances in neurological disorders · 2025Review
- Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis.Research square · 2024Article
- Addition of α-synuclein aggregates to the intestinal environment recapitulates Parkinsonian symptoms in model systems.Acta pharmacologica Sinica · 2024Article
- The Endotoxin Hypothesis of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023Review
- Article
- Opposing effects of β-2 and β-1 adrenergic receptor signaling on neuroinflammation and dopaminergic neuron survival in α-synuclein-mediated neurotoxicity.Journal of neuroinflammation · 2023Article
- Dysfunction of the noradrenergic system drives inflammation, α-synucleinopathy, and neuronal loss in mouse colon.Frontiers in immunology · 2023Article
- The Molecular Gut-Brain Axis in Early Brain Development.International journal of molecular sciences · 2022Review
- Intestinal Permeability, Dysbiosis, Inflammation and Enteric Glia Cells: The Intestinal Etiology of Parkinson's Disease.Aging and disease · 2022Article
- Article
- Inflaming the Brain with Iron.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study examined the genetic mutation and toxicant exposure in producing gut microbiota alteration and neurotoxicity. Homozygous α-synuclein mutant (SNCA) mice that overexpress human A53T protein and littermate wild-type mice received a single injection of LPS (2 mg/kg) or a selective norepinephrine depleting toxin DSP-4 (50 mg/kg), then the motor activity, dopaminergic neuron loss, colon gene expression and gut microbiome were examined 13 months later. LPS and DSP-4 decreased rotarod and wirehang activity, reduced dopaminergic neurons in substantia nigra pars compacta (SNpc), and SNCA mice were more vulnerable. SNCA mice had 1,000-fold higher human SNCA mRNA expression in the gut, and twofold higher gut expression of NADPH oxidase (NOX2) and translocator protein (TSPO). LPS further increased expression of TSPO and IL-6 in SNCA mice. Both LPS and DSP-4 caused microbiome alterations, and SNCA mice were more susceptible. The altered colon microbiome approximated clinical findings in PD patients, characterized by increased abundance of Verrucomicrobiaceae, and decreased abundance of Prevotellaceae, as evidenced by qPCR with 16S rRNA primers. The Firmicutes/Bacteroidetes ratio was increased by LPS in SNCA mice. This study demonstrated a critical role of α-synuclein and toxins interactions in producing gut microbiota disruption, aberrant gut pro-inflammatory gene expression, and dopaminergic neuron loss.
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