ArticleNeurobiology of disease2024
Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions.
Article in Neurobiology of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- Single cell and spatial atlas of macrophage and astrocyte interactions in glioblastoma.Discover oncology · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Molecular Mechanisms of Mangiferin on Neuroinflammation for Treating Major Depressive Disorder Based on Network Pharmacology and Bioinformatics Analysis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Integrative analysis via bioinformatics and machine learning identifies SERPING1 as a biomarker candidate for major depressive disorder.BMC psychiatry · 2026Article
- Neuroimmune Interactions in Neurodegeneration: The Role of Microglia in Alzheimer's and Parkinson's Disease Pathogenesis.Brain sciences · 2026Review
- Sphingolipid-Neuroinflammation Axis in Parkinson's Disease: Focus on S1P/SPHK1-NF‑κB Signaling.Journal of inflammation research · 2026Review
- Astrocytes in Parkinson's Disease: From Guardians to Accomplices.Clinical interventions in aging · 2026Review
- Regulatory T cells promote microglia-mediated synapse engulfment and functional recovery via the OPN-CD74 axis after spinal cord injury in mice.Journal of neuroinflammation · 2025Article
- Pathological α-synuclein dysregulates epitranscriptomic writer METTL3 to drive neuroinflammation in microglia.Cell reports · 2025Article
- Intrastriatal injection of alpha-synuclein preformed fibrils to rats results in L-DOPA reversible sensorimotor impairments and alterations in non-motor function.Frontiers in neuroscience · 2025Article
- From mechanisms to therapies: the multifaceted roles of guanylate-binding protein 2 in immunity, cancer, and beyond.Frontiers in immunology · 2025Review
- Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition.Journal of neuroinflammation · 2024Article
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8 authors at 2 institutions in 1 country.
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Abstract
Parkinson's disease (PD) pathology is characterized by alpha-synuclein (α-syn) aggregates, degeneration of dopamine neurons in the substantia nigra pars compacta (SNpc), and neuroinflammation. The presence of reactive glia correlates with deposition of pathological α-syn in early-stage PD. Thus, understanding the neuroinflammatory response of microglia and astrocytes to synucleinopathy may identify therapeutic targets. Here we characterized the neuroinflammatory gene expression profile of reactive microglia and astrocytes in the SNpc during early synucleinopathy in the rat α-syn pre-formed fibril (PFF) model. Rats received intrastriatal injection of α-syn PFFs and expression of immune genes was quantified with droplet digital PCR (ddPCR), after which fluorescent in situ hybridization (FISH) was used to localize gene expression to microglia or astrocytes in the SNpc. Genes previously associated with reactive microglia (Cd74, C1qa, Stat1, Axl, Casp1, Il18, Lyz2) and reactive astrocytes (C3, Gbp2, Serping1) were significantly upregulated in the SN of PFF injected rats. Localization of gene expression to SNpc microglia near α-syn aggregates identified a unique α-syn aggregate microglial gene expression profile characterized by upregulation of Cd74, Cxcl10, Rt-1a2, Grn, Csf1r, Tyrobp, C3, C1qa, Serping1 and Fcer1g. Importantly, significant microglial upregulation of Cd74 and C3 were only observed following injection of α-syn PFFs, not α-syn monomer, confirming specificity to α-syn aggregation. Serping1 expression also localized to astrocytes in the SNpc. Interestingly, C3 expression in the SNpc localized to microglia at 2- and 4-months post-PFF, but to astrocytes at 6-months post-PFF. We also observed expression of Rt1-a2 and Cxcl10 in SNpc dopamine neurons. Cumulatively our results identify a dynamic, yet reproducible gene expression profile of reactive microglia and astrocytes associated with early synucleinopathy in the rat SNpc.
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