ArticleSignal transduction and targeted therapy2022
Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus.
Article in Signal transduction and targeted therapy, 2022. 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 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Integrative Transcriptomic Analysis Reveals Impaired Oligodendrocyte Maturation and Myelination Signature in the Hippocampus of a Murine Model of Neuropsychiatric Lupus.International journal of molecular sciences · 2026Article
- Quantum and nanoscale sensing of microinflammation for earlier detection of chronic inflammatory and neuroimmune disease.Discover nano · 2026Review
- Article
- Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.Journal of advanced research · 2026Article
- Aberrant astroglial Kir4.1 activation in the anterior cingulate cortex disrupts neuronal excitability and social behavior.Acta pharmaceutica Sinica. B · 2026Article
- Time-Restricted Feeding Alters Behavior in a Sex-Specific Manner in Mice With Neuropathic Pain.Molecular nutrition & food research · 2026Article
- Ozone-induced cognitive deficits are mediated by the liver-brain axis: peripheral complement C3 triggers microglial synaptic phagocytosis.Journal of neuroinflammation · 2026Article
- Intrathecal injection of rituximab inhibits microglial M1 polarisation to alleviate neuropsychiatric SLE symptoms via the cAMP/PKA/CREB signalling pathway.Lupus science & medicine · 2026Article
- Downregulation of neuronal DRD2 drives microglia synaptic pruning and results in cognitive deficits by promoting CCL2 release in a rat model of chronic migraine.The journal of headache and pain · 2026Article
- Gut metabolite indole-3-acetic acid aggravates neuropsychiatric lupus via the AHR/STAT3 pathway in microglia.Communications biology · 2026Article
- Biomimetic nanovesicles decorated with chemotactic and target membrane proteins for lupus nephritis treatment.Journal of nanobiotechnology · 2026Article
- Inhibition of neutrophil infiltration and NETs formation ameliorates neuropsychiatric and renal dysfunction in MRL/lpr mice with lupus.PloS one · 2026Article
- IFNγ-associated immune-metabolic remodeling is linked to serotonin-kynurenine imbalance and cortical vulnerability in lupus-prone mice.Frontiers in immunology · 2026Article
- A Nomogram Predicting the Risk of Anxiety in Third-Trimester pregnancy in Pregnant Women with CTDs.Journal of multidisciplinary healthcare · 2026Article
- Review
- From injury to recovery: transcriptomic dynamics in zebrafish brain regeneration.Journal of translational medicine · 2025Article
- Glucocorticoid-mediated suppression of the CCL2-CCR2 axis drives monocyte dysfunction in severe pneumonia among immunocompromised hosts.Respiratory research · 2025Article
- Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.Molecular psychiatry · 2025Article
- Maladaptive Neuroplasticity Under Stress: Insights into Neuronal and Synaptic Changes in the Prefrontal Cortex.Molecular neurobiology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropsychiatric lupus (NPSLE) is a frequent manifestation of systemic lupus erythematosus (SLE) that occurs in 40-90% of SLE patients; however, the underlying mechanisms remain elusive, causing a severe lack of therapeutic targets for this condition. Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology. In the lupus brain, C1q was increased and localized at synaptic terminals, causing the apposition of phagocytic microglia and ensuing synaptic engulfment. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic deposition and subsequent microglia-mediated synaptic elimination. Minocycline-mediated deactivation of microglia, antibody blockade of C1q, or neuronal restoration of Nr4a1 protected lupus mice from synapse loss and NP manifestations. Our findings revealed an active role of neurons in coordinating microglia-mediated synaptic loss and highlighted neuronal Nr4a1 and C1q as critical components amenable to therapeutic intervention in NPSLE.
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