Department of Physiology and Pharmacology, City University of New York Medical School, New York, New York, USA.
Biol Psychiatry. 2010 Mar 15;67(6):558-66. doi: 10.1016/j.biopsych.2009.12.008.
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.
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).
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.
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.
据推测，与自身免疫性疾病相关的大脑炎症过程可能是情绪障碍的致病因素。因此，我们检查了自身免疫倾向细胞因子 B 细胞激活因子 (BAFF) 转基因小鼠的情绪行为，该模型可模拟系统性红斑狼疮、类风湿关节炎和干燥综合征。
我们对一系列男性 BAFF 转基因小鼠进行了标准的情绪行为检测。还对这些小鼠进行了大脑炎症、应激诱导的 c-Fos 表达、海马祖细胞增殖以及海马依赖性和非依赖性长时程增强（LTP）检测。
我们的研究表明，年老的 BAFF 转基因小鼠表现出与大脑炎症相关的焦虑样表型。此外，焦虑的小鼠在应对轻度焦虑刺激时，其边缘系统的神经元激活异常。在焦虑的 BAFF 转基因小鼠中，成年海马齿状回颗粒下区的新神经元增殖明显减少，并且还显示出依赖于神经发生和非依赖于神经发生的齿状回 LTP 受损。
我们的结果表明，与系统性红斑狼疮、类风湿关节炎和干燥综合征等自身免疫性疾病相关的焦虑可能与大脑炎症、神经发生受损和海马可塑性有关。BAFF 转基因小鼠可用于未来的研究，以测试具有治疗价值的化合物，用于治疗与自身免疫性疾病相关的情绪障碍。
