Reduced adult neurogenesis and altered emotional behaviors in autoimmune-prone B-cell activating factor transgenic mice

Biol Psychiatry. 2010 Mar 15;67(6):558-66. doi: 10.1016/j.biopsych.2009.12.008.

Abstract

Background: It has been postulated that brain inflammatory processes associated with autoimmune diseases may be causative factors in emotional disorders. Accordingly, we examined emotional behaviors in autoimmune-prone cytokine B-cell-activating factor (BAFF) transgenic mice, a model of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome.

Methods: Male BAFF transgenic mice were examined on a series of standard laboratory assays of emotionality. Mice were also tested for brain inflammation, stress-induced c-Fos expression, hippocampal progenitor cell proliferation, and hippocampal neurogenesis-dependent and neurogenesis-independent long-term potentiation (LTP).

Results: Our study revealed that older BAFF transgenic mice exhibit an anxiety-like phenotype associated with brain inflammation. Furthermore, anxious mice display an abnormal neuronal activation within the limbic system in response to mild anxiogenic stimuli. Proliferation of newly formed neurons in the subgranular zone of adult hippocampus was significantly decreased in anxious BAFF transgenic mice that also showed impaired neurogenesis-dependent and neurogenesis-independent dentate gyrus LTP.

Conclusions: Our results suggest that anxiety associated with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome can be linked to brain inflammation, impaired neurogenesis, and hippocampal plasticity. BAFF transgenic mice can be used in future studies to test compounds of therapeutic value for the treatment of mood disorders associated with autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Anxiety* / genetics
  • Anxiety* / pathology
  • Anxiety* / physiopathology
  • B-Cell Activating Factor / genetics*
  • Behavior, Animal / physiology
  • Cell Proliferation
  • Disease Models, Animal
  • Electric Stimulation / methods
  • Emotions / physiology*
  • Encephalitis* / genetics
  • Encephalitis* / pathology
  • Encephalitis* / physiopathology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Exploratory Behavior / physiology
  • Gene Expression Regulation / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Hindlimb Suspension / methods
  • Hippocampus / cytology
  • Immunoglobulin G / blood
  • In Vitro Techniques
  • Long-Term Potentiation / genetics
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / genetics*
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Stem Cells / physiology
  • Swimming / psychology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B-Cell Activating Factor
  • CD68 antigen, human
  • Glial Fibrillary Acidic Protein
  • Immunoglobulin G
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Proto-Oncogene Proteins c-fos
  • doublecortin protein