title: Reduced adult neurogenesis and altered emotional behaviors in autoimmune-prone B-cell activating factor transgenic mice.
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.
authors.affiliation: Department of Physiology and Pharmacology, City University of New York Medical School, New York, New York, USA.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.forename: Marco
authors.initials: M
authors.lastname: Cambiaghi
authors.forename: Linda
authors.initials: L
authors.lastname: Spatz
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.forename: Mitchell
authors.initials: M
authors.lastname: Thorn
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
authors.forename: Fortunato
authors.initials: F
authors.lastname: Battaglia
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001007:Anxiety / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D053264:B-Cell Activating Factor / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004558:Electric Stimulation / Q000379:methods; D004644:Emotions / Q000502:physiology*; D004660:Encephalitis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019417:Hindlimb Suspension / Q000379:methods; D006624:Hippocampus / Q000166:cytology; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013550:Swimming / Q000523:psychology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053264:B-Cell Activating Factor; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; C067980:CD68 antigen, human; D000097382:CD68 Molecule