ArticleExperimental neurology2011
Neuroprotective and neurodegenerative effects of the chronic expression of tumor necrosis factor α in the nigrostriatal dopaminergic circuit of adult mice.
Article in Experimental neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
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- Dapagliflozin ameliorates motor deficits in a Parkinson's disease model induced by 6-OHDA: An integrative in vivo and in silico approach from α-synuclein/A2AAR/TH/TNF-α to APAF-1/caspase-3 modulation.Inflammopharmacology · 2026Article
- Cortical White and Grey Matter Volume Differences Associated with Plasma Cytokine and Chemokine Levels in PLWH in Cape Town.International journal of molecular sciences · 2025Article
- The Dual Role of Survival Genes in Neurons and Cancer Cells: a Strategic Clinical Application of DX2 in Neurodegenerative Diseases and Cancer.Biomolecules & therapeutics · 2025Review
- Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson's Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice.Molecular neurobiology · 2024Article
- Identification of immune-related hub genes in spinal cord injury.European journal of medical research · 2024Article
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- Cytokine activity in Parkinson's disease.Neuronal signaling · 2023Review
- Evaluation of the therapeutic potential of cerebrolysin and/or lithium in the male Wistar rat model of Parkinson's disease induced by reserpine.Metabolic brain disease · 2023Article
- A systematic review and meta-analysis of inflammatory biomarkers in Parkinson's disease.NPJ Parkinson's disease · 2023Review
- Naringin Attenuates the Diabetic Neuropathy in STZ-Induced Type 2 Diabetic Wistar Rats.Life (Basel, Switzerland) · 2022Article
- Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia.Cells · 2022Article
- CanJournal of parasitology research · 2020Article
- P2X4R Overexpression Upregulates Interleukin-6 and Exacerbates 6-OHDA-Induced Dopaminergic Degeneration in a Rat Model of PD.Frontiers in aging neuroscience · 2020Article
- Cytokine-, Neurotrophin-, and Motor Rehabilitation-Induced Plasticity in Parkinson's Disease.Neural plasticity · 2020Review
- Parkinson's Disease With Depression: The Correlations Between Neuroinflammatory Factors and Neurotransmitters in Cerebrospinal Fluid.Frontiers in aging neuroscience · 2020Article
- TNFα inhibitors as targets for protective therapies in MSA: a viewpoint.Journal of neuroinflammation · 2019Review
- A New Venue of TNF Targeting.International journal of molecular sciences · 2018Review
- Acute Neuroinflammatory Response in the Substantia Nigra Pars Compacta of Rats after a Local Injection of Lipopolysaccharide.Journal of immunology research · 2018Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine, has been implicated in both neuronal death and survival in Parkinson's disease (PD). The substantia nigra (SN), a CNS region affected in PD, is particularly susceptible to inflammatory insults and possesses the highest density of microglial cells, but the effects of inflammation and in particular TNF-α on neuronal survival in this region remains controversial. Using adenoviral vectors, the CRE/loxP system and hypomorphic mice, we achieved chronic expression of two levels of TNF-α in the SN of adult mice. Chronic low expression of TNF-α levels reduced the nigrostriatal neurodegeneration mediated by intrastriatal 6-hydroxydopamine administration. Protective effects of low TNF-α level could be mediated by TNF-R1, GDNF, and IGF-1 in the SN and SOD activity in the striatum (ST). On the contrary, chronic expression of high levels of TNF-α induced progressive neuronal loss (63% at 20 days and 75% at 100 days). This effect was accompanied by gliosis and an inflammatory infiltrate composed almost exclusively by monocytes/macrophages. The finding that chronic high TNF-α had a slow and progressive neurodegenerative effect in the SN provides an animal model of PD mediated by the chronic expression of a single cytokine. In addition, it supports the view that cytokines are not detrimental or beneficial by themselves, i.e., their level and time of expression among other factors can determine its final effect on CNS damage or protection. These data support the view that new anti-parkinsonian treatments based on anti-inflammatory therapies should consider these dual effects of cytokines on their design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.