Background: Systemic lupus erythematosus (SLE) frequently affects the central nervous system, causing cognitive and motor impairments whose mechanisms remain unclear. Neuroinflammation is a hallmark of neuropsychiatric SLE, but upstream factors shaping central nervous system (CNS) vulnerability are not fully defined. Pristane exposure induces an SLE-like phenotype with autoantibody production, heightened inflammation, and behavioral changes paralleling lupus patients. Emerging evidence indicates that gut microbial dysbiosis modulates microglial activation, glutamatergic synaptic integrity, and dopaminergic circuit function through immune–metabolic signaling, supporting a gut–immune–brain axis in lupus neurobiology. HypothesisWe hypothesized that pristane-induced autoimmunity reshapes gut microbial communities in ways that amplify neuroimmune activation, impair hippocampal glutamatergic and nigrostriatal dopaminergic circuits, and culminate in cognitive–motor dysfunction. ObjectiveTo define how pristane-induced SLE alters cognitive–motor behavior and to identify convergent changes across neuroimmune markers, synaptic and dopaminergic integrity, and gut microbiome structure. Methods: Female BALB/cAJcl mice received intraperitoneal injections of 0. 5 mL saline (n = 13) or pristane (n = 15). After four months, motor and cognitive function were assessed using the Open Field Test and Novel Object Recognition, and cognitive–motor integration was measured via the Pole Test. SLE induction was confirmed by elevated anti-dsDNA antibodies, increased IL-6, and splenomegaly (all p < 0. 001). Hippocampal and substantia nigra tissues were analyzed for VGLUT1, TH, Iba-1, and GFAP. Fecal samples underwent 16S rDNA Nanopore sequencing with alpha/beta diversity and LEfSe analyses. Results: Pristane-treated mice showed significant impairments in Pole Test turn and descent times (both p < 0. 05), whereas Open Field and Novel Object Recognition outcomes were unchanged. Pole Test deficits coincided with reduced hippocampal VGLUT1 (p < 0. 001), consistent with impaired glutamatergic signaling, and decreased TH-positive neurons in the substantia nigra (p < 0. 01), indicating disrupted dopaminergic pathways. Robust microglial and astrocytic activation (all p < 0. 001) further supported neuroimmune involvement. Microbiome profiling revealed unchanged alpha diversity but modest beta-diversity differences (p = 0. 012). LEfSe identified pristane-enriched taxa such as Clostridium xylanovorans and Intestinimonas butyriciproducens, while saline-treated mice had higher levels of Parabacteroides merdae, Alistipes putredinis, and Ruminococcus torques, suggesting a shift from a commensal-rich, anti-inflammatory ecosystem toward dysbiosis permissive to systemic inflammation and impaired gut–brain communication. Conclusion: Pristane-induced autoimmunity disrupts neural circuits, activates neuroimmune pathways, and remodels the gut microbiome, supporting a mechanistically integrated gut–immune–brain axis contributing to neuropsychiatric SLE. These findings highlight microbiome-driven neuroimmune mechanisms as candidate targets for mitigating CNS complications in lupus. Funding: Chulalongkorn University Fundamental Fund (Grant No. HEAFF₆8₂75₃000₀41) ; Quick Win Research Project Ratchadapiseksompotch Fund, Chulalongkorn University (Grant No. 767006). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Karapanon et al. (Fri,) studied this question.