ArticleJournal of neuroinflammation2023
SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.International journal of molecular sciences · 2026Article
- Neuroprotective and Antidepressant Effects ofExperimental neurobiology · 2026Article
- Association between influenza A virus and SARS-CoV-2 infections and mood disorders.Brain, behavior, & immunity - health · 2026Article
- Mild chronic hypoxia and the brain: an ambiguous relationship.Journal of neuroinflammation · 2026Review
- Neuroimmune pathophysiology of long COVID.Psychiatry and clinical neurosciences · 2025Review
- The SARS-CoV-2 envelope PDZ binding motif acts as a virulence factor disrupting host's epithelial cell-cell junctions.Cellular & molecular biology letters · 2025Article
- Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation.Journal of neuroinflammation · 2025Review
- TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.Current medicinal chemistry · 2025Review
- TLR2/NF-κB signaling in macrophage/microglia mediated COVID-pain induced by SARS-CoV-2 envelope protein.iScience · 2024Article
- Reactive Astrocytosis-A Potential Contributor to Increased Suicide in Long COVID-19 Patients?Brain sciences · 2024Review
- Special Issue "The Role of Toll-Like Receptors (TLRs) in Infection and Inflammation 2.0".International journal of molecular sciences · 2024Article
- Neurological Impact of Respiratory Viruses: Insights into Glial Cell Responses in the Central Nervous System.Microorganisms · 2024Review
- Exploring viral neuropathic pain: Molecular mechanisms and therapeutic implications.PLoS pathogens · 2024Review
- Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19.Annual review of immunology · 2024Review
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Navigating the Complex Terrain of Dysregulated Microglial Function in Depressive Disorders: Insights, Challenges and Future Directions.Aging and disease · 2024Review
- IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve.Journal of neuroinflammation · 2024Article
- Multifaceted role of SARS-CoV-2 structural proteins in lung injury.Frontiers in immunology · 2024Review
- SARS-CoV-2 Omicron Variants Show Attenuated Neurovirulence Compared with the Wild-Type Strain in Elderly Human Brain Spheroids.Research (Washington, D.C.) · 2024Article
- SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.Apoptosis : an international journal on programmed cell death · 2023Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundDepression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS).
methodsDepression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice.
resultsIntracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1β, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1β, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein.
conclusionsOur study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.
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