title: Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice.
abstract: 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.
authors.affiliation: The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Ariel.stock@med.einstein.yu.edu.
authors.forename: Ariel D
authors.initials: AD
authors.lastname: Stock
authors.affiliation: The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Jing.wen@phd.einstein.yu.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Jessica.doerner@phd.einstein.yu.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Doerner
authors.affiliation: The Department of Pathology, Cleveland Clinic, Cleveland, OH, 44195, USA. Herlitl@ccf.org.
authors.forename: Leal C
authors.initials: LC
authors.lastname: Herlitz
authors.affiliation: Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Maria.gulinello@einstein.yu.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Gulinello
authors.affiliation: The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Chaim.putterman@einstein.yu.edu.|Division of Rheumatology, Albert Einstein College of Medicine, F701N, 1300 Morris Park Ave., Bronx, NY, 10461, USA. Chaim.putterman@einstein.yu.edu.
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier; D016026:Bone Marrow Transplantation; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D002678:Chimera; D002831:Choroid Plexus / Q000473:pathology; D003863:Depression / Q000523:psychology; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000523:psychology* / Q000628:therapy; D008569:Memory Disorders / Q000523:psychology; D001523:Mental Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009043:Motor Activity; D011597:Psychomotor Performance
chemical_list: D018946:Chemokine CCL5