Sex and autoantibody titers determine the development of neuropsychiatric manifestations in lupus-prone mice

J Neuroimmunol. 2010 Dec 15;229(1-2):112-22. doi: 10.1016/j.jneuroim.2010.07.020. Epub 2010 Aug 25.

Abstract

Emotional disturbances are among the most common neuropsychiatric manifestations of SLE, a systemic autoimmune disease with a strong female predominance. In this study, we evaluated young MRL/lpr mice, directly comparing males and females. MRL/lpr females exhibited significant depression as early as 5 weeks (at which time elevated levels of autoantibodies were already present), as compared to MRL/lpr males, where depression was noted only at 18 weeks. Depression was significantly correlated with autoantibodies against nuclear antigens, NMDA receptor, and ribosomal P. Our results are consistent with a primary role of autoantibodies in the pathogenesis of early neuropsychiatric deficits in this lupus model, which translate into gender-based differences in clinical phenotype.

MeSH terms

  • Analysis of Variance
  • Animals
  • Autoantibodies / blood*
  • Behavior, Animal
  • Behavioral Symptoms / etiology*
  • Cardiolipins / immunology
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Female
  • Lupus Vasculitis, Central Nervous System / blood
  • Lupus Vasculitis, Central Nervous System / complications*
  • Lupus Vasculitis, Central Nervous System / immunology*
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred MRL lpr
  • Pattern Recognition, Visual / physiology
  • Photic Stimulation / methods
  • Psychomotor Performance / physiology
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Sex Factors
  • Social Behavior
  • Swimming / psychology

Substances

  • Autoantibodies
  • Cardiolipins
  • Receptors, N-Methyl-D-Aspartate