ArticleJournal of neuroinflammation2020
T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson's disease.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Adaptive immune responses are not causal to SGN death after kanamycin-induced hair cell loss.bioRxiv : the preprint server for biology · 2026Article
- Review
- Neuroprotection of engineeredJournal of Zhejiang University. Science. B · 2026Article
- Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.Cellular and molecular neurobiology · 2026Review
- Meningeal and infiltrating T-cells are associated with repetitive head trauma and tau-mediated neurodegeneration in chronic traumatic encephalopathy.Acta neuropathologica communications · 2026Article
- Microglia-T cell interactions drive α-synuclein pathology in a Parkinson's disease mouse model.Journal of neuroinflammation · 2026Article
- Article
- Helicobacter pylori infection and α-synuclein pathology drive parallel neurodegenerative pathways in the substantia nigra.Journal of neuroinflammation · 2025Article
- Pancreatic hypersecretion of amyloid-forming human amylin dysregulates the neuro-immune axis and B cell development in a model of type-2 diabetes.Neurobiology of disease · 2025Article
- Neuroimmune crosstalk in Parkinson's disease: the pivotal role of microglia and infiltrating T cells.Molecular biology reports · 2025Review
- Transcriptomic Analysis of Immune-Related Genes in the Striatum of Parkinson's Disease Brain Across Mouse Strains.Journal of molecular neuroscience : MN · 2025Article
- Parkinson's disease: exploring the systemic immune mechanisms through molecular investigations.Inflammopharmacology · 2025Review
- Diverse cell types establish a pathogenic immune environment in peripheral neuropathy.Journal of neuroinflammation · 2025Article
- Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life.Alcohol, clinical & experimental research · 2025Article
- Article
- Article
- Aging and MPTP Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra.Cellular and molecular neurobiology · 2025Article
- Neuromodulation influences T lymphocyte calcium signaling and alpha synuclein clearance: implications for Parkinson's disease.Frontiers in cellular neuroscience · 2025Review
- Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundParkinson's disease (PD) is the second most prevalent movement disorder characterized by up to 80% loss of dopamine (DA) neurons and accumulation of Lewy body deposits composed of α-synuclein (α-syn). Accumulation of α-syn is associated with microglial activation, leading to a pro-inflammatory environment linked with the pathogenesis of PD. Along with microglia, CD4 and CD8 T cells are observed in SNpc. The contribution of T-cells to PD development remains unclear with studies demonstrating that they may mediate neurodegeneration or act in a neuroprotective manner.
methodsHere, we assessed the contribution of T cells to PD neurodegeneration using an adeno-associated virus (AAV) coding human wild-type α-syn or GFP injected into the substantia nigra pars compacta (SNpc) in T cell deficient (athymic nude) and T cell competent (heterozygous) rats. The rats were behaviorally assessed with cylinder test to test paw bias. Following behavior testing, brains were collected and analyzed for markers of dopamine neuron, microglial activation, T cells, and α-syn expression.
resultsInjection of AAV9-α-syn unilaterally into the SN of T cell competent rats resulted in a significant paw bias in comparison to the controls at 60 days post-injection. Conversely, T cell-deficient rats injected with AAV9-α-syn showed no deficit in paw bias. As expected, injected T cell competent rats demonstrated a significant increase in microglial activation (MHCII staining) as well as significant dopaminergic neuron loss. In contrast, the T cell-deficient counterparts did not show a significant increase in microglial activation or significant neuron loss compared to the control animals. We also observed CD4 and CD8 T cells in SNpc following microglial MHCII expression and dopaminergic neuron loss. The time course of T cell entry correlates with upregulation of MHCII and the peak loss of TH+ cells in the SNpc.
conclusionThese data demonstrate that T cell infiltration and microglial upregulation of MHCII are involved in α-synuclein-mediated DA neuron loss in this rat model of PD.
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