ArticleJournal of neuroinflammation2021
Microglial activation contributes to cognitive impairments in rotenone-induced mouse Parkinson's disease model.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2026Pooled it
- HMGA1 Lactylation-Mediated Regulation of the SP1/VEGFA Axis in Pathological Angiogenesis Under Diabetic Retinopathy.Diabetes · 2026Article
- Myelin-driven structural network redundancy underlies cognition in cerebral small vessel disease.Alzheimer's research & therapy · 2026Article
- The C3-C3aR axis drives rotenone-induced cognitive damage via synaptic engulfment, dark microglia and PANoptosis.Redox biology · 2026Article
- Mitochondrial DNA drives NLRP3-IL-1β axis activation in microglia by binding to NLRP3, leading to neurodegeneration in Parkinson's disease models.Cell death & disease · 2026Article
- "Unfolding Parkinson's Disease Through the Microbiome-Gut-Brain Axis".Journal of molecular neuroscience : MN · 2026Review
- Nicotinamide counteracts Rotenone-induced mitochondrial and neuronal dysfunction in a translational early-life model.Scientific reports · 2026Article
- Neuroinflammation at the Crossroads of Neurodegeneration: The Roles of Microglia and Astrocytes in Parkinson's Disease, Alzheimer's Disease, and Multiple Sclerosis.Neurosciences (Riyadh, Saudi Arabia) · 2026Review
- Primary Human Reactive Microglia Display Mitochondrial Dysfunction and Metabolic Imbalance Upon Lipopolysaccharide Exposure.Neurochemical research · 2026Article
- Berberine Alleviates Lipopolysaccharide-Induced Impairments in Neuroplasticity and Spatial Memory by Modulating Microglial Polarization via MAPK Signaling Inhibition.Neural plasticity · 2026Article
- Nanotherapeutic Interventions for Parkinson's Disease: Modulating Pathogenic Mechanisms and Overcoming Therapeutic Obstacles.International journal of nanomedicine · 2026Review
- Inflammatory mechanisms contribute to long-term cognitive deficits induced by perinatal asphyxia via interleukin-1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Realization of differential release of minocycline hydrochloride from electrosprayed polymeric or biomacromolecular microparticles for the repair of traumatic brain injury.Materials today. Bio · 2025Article
- Irisin inhibits dopaminergic neuron lactate metabolism and repairs mitochondrial function to alleviate Parkinson's disease by activating SIRT1 signaling pathway.Communications biology · 2025Article
- Effects ofJournal of microbiology and biotechnology · 2025Article
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Microglial deficiency in the ATRX chromatin remodeler elicits a viral mimicry immune response that impacts neuronal function and behavior.PLoS biology · 2025Article
- Bridging regional neurovascular unit heterogeneity and cognitive function: a review.Fluids and barriers of the CNS · 2025Review
- Wilms Tumor 1 Associated Protein (WTAP) Inhibits Inflammation Provoked by Mycobacterium tuberculosis in Microglial BV-2 Cells and Promotes Differentiation of Neural Stem/Progenitor Cells into Neurons by Elevating Expression of HMGN3 Protein Resulted from Modulation of mBulletin of experimental biology and medicine · 2025Article
- The efficacy and pharmacological mechanism of Guilingji to prevent Alzheimer's disease.Alzheimer's research & therapy · 2025Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCognitive decline occurs frequently in Parkinson's disease (PD), which greatly decreases the quality of life of patients. However, the mechanisms remain to be investigated. Neuroinflammation mediated by overactivated microglia is a common pathological feature in multiple neurological disorders, including PD. This study is designed to explore the role of microglia in cognitive deficits by using a rotenone-induced mouse PD model.
methodsTo evaluate the role of microglia in rotenone-induced cognitive deficits, PLX3397, an inhibitor of colony-stimulating factor 1 receptor, and minocycline, a widely used antibiotic, were used to deplete or inactivate microglia, respectively. Cognitive performance of mice among groups was detected by Morris water maze, objective recognition, and passive avoidance tests. Neurodegeneration, synaptic loss, α-synuclein phosphorylation, glial activation, and apoptosis were determined by immunohistochemistry and Western blot or immunofluorescence staining. The gene expression of inflammatory factors and lipid peroxidation were further explored by using RT-PCR and ELISA kits, respectively.
resultsRotenone dose-dependently induced cognitive deficits in mice by showing decreased performance of rotenone-treated mice in the novel objective recognition, passive avoidance, and Morris water maze compared with that of vehicle controls. Rotenone-induced cognitive decline was associated with neurodegeneration, synaptic loss, and Ser129-phosphorylation of α-synuclein and microglial activation in the hippocampal and cortical regions of mice. A time course experiment revealed that rotenone-induced microglial activation preceded neurodegeneration. Interestingly, microglial depletion by PLX3397 or inactivation by minocycline significantly reduced neuronal damage and α-synuclein pathology as well as improved cognitive performance in rotenone-injected mice. Mechanistically, PLX3397 and minocycline attenuated rotenone-induced astroglial activation and production of cytotoxic factors in mice. Reduced lipid peroxidation was also observed in mice treated with combined PLX3397 or minocycline and rotenonee compared with rotenone alone group. Finally, microglial depletion or inactivation was found to mitigate rotenone-induced neuronal apoptosis.
conclusionsTaken together, our findings suggested that microglial activation contributes to cognitive impairments in a rotenone-induced mouse PD model via neuroinflammation, oxidative stress, and apoptosis, providing novel insight into the immunopathogensis of cognitive deficits in PD.
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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.