期刊
HIPPOCAMPUS
卷 14, 期 5, 页码 649-661出版社
WILEY
DOI: 10.1002/hipo.10205
关键词
autoimmunity; inflammation; lupus; hippocampus; Fluoro Jade B; ubiquitin; spontaneous alternation behavior; cyclophosphamide; MRL mice
资金
- NIAMS NIH HHS [R21 AR049163-01, 1R21 AR49163-01, R21 AR049163] Funding Source: Medline
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R21AR049163] Funding Source: NIH RePORTER
Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-Ipr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro jade B (FIB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the reversal trial were impaired in diseased MRL-Ipr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FIB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FIB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. (C) 2004 Wiley-Liss, Inc.
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