Reduced adult neurogenesis and altered emotional behaviors in autoimmune-prone B-cell activating factor transgenic mice.
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.
Crupi
Rosalia
R
Department of Physiology and Pharmacology, City University of New York Medical School, New York, New York, USA.
Cambiaghi
Marco
M
Spatz
Linda
L
Hen
René
R
Thorn
Mitchell
M
Friedman
Eitan
E
Vita
Giuseppe
G
Battaglia
Fortunato
F
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
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