Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system

Arthritis Rheum. 2007 Mar;56(3):938-48. doi: 10.1002/art.22419.


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-injected 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / pharmacology*
  • Antidepressive Agents, Second-Generation / pharmacology
  • Autoimmunity / immunology*
  • Brain / immunology
  • Brain / pathology
  • Cognition / drug effects
  • Cognition / physiology
  • Depression / etiology
  • Depression / immunology*
  • Disease Models, Animal
  • Female
  • Fluoxetine / pharmacology
  • Haloperidol / pharmacology
  • Limbic System / drug effects
  • Limbic System / immunology*
  • Lupus Erythematosus, Systemic / complications
  • Mice
  • Mice, Inbred C3H
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Physical Exertion / physiology
  • Ribosomal Proteins / immunology*
  • Rotarod Performance Test


  • Antibodies, Anti-Idiotypic
  • Antidepressive Agents, Second-Generation
  • Ribosomal Proteins
  • Fluoxetine
  • Haloperidol