Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice

Journal of Neuroinflammation

Chaim Putterman²  Maria Gulinello¹  Leal C. Herlitz⁴  Jessica Doerner³  Jing Wen³  Ariel D. Stock³ 

[1] Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx 10461, NY, USA;Division of Rheumatology, Albert Einstein College of Medicine, F701N, 1300 Morris Park Ave., Bronx 10461, NY, USA;The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx 10461, NY, USA;The Department of Pathology, Cleveland Clinic, Cleveland 44195, OH, USA

关键词: Autoantibodies;    Bone marrow transplantation;    Neuropsychiatric SLE;    SLE;    Lupus;   

Others  :  1234439
DOI  :  10.1186/s12974-015-0423-4

 received in 2015-08-30, accepted in 2015-10-27,  发布年份 2015

【 摘 要 】

Background

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40 % of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors.

Methods

To dissect the relative contributions of the central nervous system from those of the hematopoietic compartment, we generated bone marrow chimeras between healthy control (MRL/+) and lupus-prone MRL/Tnfrsf6 ^lpr/lpr mice (MRL/+ → MRL/lpr), as well as control chimeras. After bone marrow reconstitution, mice underwent extensive behavioral testing, analysis of brain tissue, and histological assessment.

Results

Despite transfer of healthy MRL/+ bone marrow and marked attenuation of systemic disease, we found that MRL/+ → MRL/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits, comparable to MRL/lpr → MRL/lpr control transplanted mice and the behavioral profile previously established in MRL/lpr mice. Moreover, MRL/+ → MRL/lpr chimeric mice displayed increased brain RANTES expression, neurodegeneration, and cellular infiltration in the choroid plexus, as well as blood brain barrier disruption, all in the absence of significant systemic autoimmunity.

Conclusions

Chimeric MRL/+ → MRL/lpr mice displayed no attenuation of the behavioral phenotype found in MRL/lpr mice, despite normalized serum autoantibodies and conserved renal function. Therefore, neuropsychiatric disease in the MRL/lpr lupus-prone strain of mice can occur absent any major contributions from systemic autoimmunity.

【 授权许可】

   
2015 Stock et al.

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