Neural Mechanisms of Neuropsychiatric Lupus
Abstract
This is the final report for project number W81XWH-19-1-0759. It addresses neuropsychiatric systemic lupus erythematosus (NPSLE), a constellation of syndromes that affects the nervous system in subjects with lupus. A major manifestation of NPSLE is impaired cognition. This project has studied brain-related processes in murine models of lupus, with the goal of identifying brain-based biomarkers for NPSLE progression. We have tested the hypothesis that impaired cognition in NPSLE originates from synaptic and network imbalances in the brains cognitive centers, particularly the hippocampus. Therefore, this project has determined the effect of lupus antibodies on cognitive behaviors, synaptic function, and ensemble patterns in the hippocampus. We further hypothesize that the damage inflicted by specific lupus antibodies (which we test with autoantibody-based mouse models) is exacerbated by the presence of inflammatory cytokines that are also present in SLE subjects (which we test with spontaneous lupus models). Our approach is innovative, as we study neurophysiological signals, recorded in brain regions that are the neural substrate for cognition, in NPSLE murine models. Since the current therapeutic strategies to treat NPSLE are largely immunosuppressive, novel approaches such as brain-based biomarkers are urgently needed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1203045
Entities
People
- Patricio Huerta
Organizations
- The Feinstein Institute for Medical Research