TY - JOUR
T1 - Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system
AU - Katzav, Aviva
AU - Solodeev, Inna
AU - Brodsky, Ori
AU - Chapman, Joab
AU - Pick, Chaim G.
AU - Blank, Miri
AU - Zhang, Wei
AU - Reichlin, Morris
AU - Shoenfeld, Yehuda
N1 - Funding Information:
Acknowledgement This study was supported, in part, by the Japanese government, Ministry of Education, Culture, Sports, Science, and Technology, awarded to Dr. Tazuma (No. 12670489).
PY - 2007/3
Y1 - 2007/3
N2 - Objective. Autoantibodies against ribosomal P proteins are linked to the neuropsychiatric manifestations of systemic lupus erythematosus (SLE). The present study was undertaken to assess how the specific brain-binding autoantibody anti-ribosomal P can induce a depression-type psychiatric disorder in mice. Methods. Mice were injected intracerebroventricularly with affinity-purified human anti-ribosomal P antibodies or IgG as control. Pharmacologic and immunologic treatments included the antidepressant drug fluoxetine, the antipsychotic drug haloperidol, and antiidiotypic antibodies. Behavior was assessed by the forced swimming test, motor deficits by rotarod, grip strength, and staircase tests, and cognitive deficits by T-maze alternation and passive avoidance tests. Results. Anti-ribosomal P antibodies induced depression-like behavior in the mice (mean ± SEM 147.3 ± 19.2 seconds of immobility versus 75.2 ± 12.1 seconds of immobility in IgG-infected control mice; P < 0.005). The anti-ribosomal P antibody-induced depression-like behavior was partially blocked by a specific antiidiotypic antibody and significantly blocked by long-term treatment with fluoxetine, but not by short-or long-term treatment with haloperidol. The depressive behavior was not associated with any motor or cognitive deficits. Anti-ribosomal P antibodies specifically stained neurons in the hippocampus, cingulate cortex, and the primary olfactory piriform cortex, compatible with the previously described binding to the membrane-bound P0 ribosomal protein. Conclusion. This is the first report of an experimental depression induced by a specific autoantibody. The results implicate olfactory and limbic areas in the pathogenesis of depression in general, and in central nervous system dysfunction in SLE in particular.
AB - Objective. Autoantibodies against ribosomal P proteins are linked to the neuropsychiatric manifestations of systemic lupus erythematosus (SLE). The present study was undertaken to assess how the specific brain-binding autoantibody anti-ribosomal P can induce a depression-type psychiatric disorder in mice. Methods. Mice were injected intracerebroventricularly with affinity-purified human anti-ribosomal P antibodies or IgG as control. Pharmacologic and immunologic treatments included the antidepressant drug fluoxetine, the antipsychotic drug haloperidol, and antiidiotypic antibodies. Behavior was assessed by the forced swimming test, motor deficits by rotarod, grip strength, and staircase tests, and cognitive deficits by T-maze alternation and passive avoidance tests. Results. Anti-ribosomal P antibodies induced depression-like behavior in the mice (mean ± SEM 147.3 ± 19.2 seconds of immobility versus 75.2 ± 12.1 seconds of immobility in IgG-infected control mice; P < 0.005). The anti-ribosomal P antibody-induced depression-like behavior was partially blocked by a specific antiidiotypic antibody and significantly blocked by long-term treatment with fluoxetine, but not by short-or long-term treatment with haloperidol. The depressive behavior was not associated with any motor or cognitive deficits. Anti-ribosomal P antibodies specifically stained neurons in the hippocampus, cingulate cortex, and the primary olfactory piriform cortex, compatible with the previously described binding to the membrane-bound P0 ribosomal protein. Conclusion. This is the first report of an experimental depression induced by a specific autoantibody. The results implicate olfactory and limbic areas in the pathogenesis of depression in general, and in central nervous system dysfunction in SLE in particular.
UR - http://www.scopus.com/inward/record.url?scp=33947175115&partnerID=8YFLogxK
U2 - 10.1002/art.22419
DO - 10.1002/art.22419
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AN - SCOPUS:33947175115
SN - 0004-3591
VL - 56
SP - 938
EP - 948
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 3
ER -