Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to the collection of syndromes, ranging from psychosis to memory problems, which target the brain of 40-90% of subjects with lupus. Crucially, DNRAbs are lupus antibodies that bind DNA and cross-react with the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor. There is now compelling evidence for the pathogenic role of DNRAbs in NPSLE suggesting that these antibodies can cause memory dysfunction.
We have studied a mouse model of NPSLE in which animals carry DNRAbs, which enter the brain after a temporary disruption of the blood-brain barrier. We call this model "DNRAb+ mice" and they show spatial impairment that we measure with the object-place memory (OPM) task. DNRAb+ and DNRAb– (control) mice were implanted with tetrode arrays targeting the CA1 region of the hippocampus, which is a crucial brain substrate for spatial encoding. In vivo electrophysiology recordings were conducted during the OPM task to study place cells as well as power spectral densities of network oscillations.
We found abnormal place cell properties in the DNRAb+ mice, such as expanded place field size, reduced stability, and lower spatial information when compared to DNRAb– mice. Moreover, we found significantly altered co-modulation of theta-gamma oscillations when the mice examined objects moved to novel locations.
Our behavioral and electrophysiological studies reveal disruptions in healthy place cell dynamics and oscillatory patterns by DNRAbs that may explain the abnormalities in spatial encoding that occur in NPSLE. Our data offer a substrate for brain-based biomarkers aimed at alleviating NPSLE-related cognitive impairment.