Reduced Adult Neurogenesis and Altered Emotional Behaviors in Autoimmune-Prone B-Cell Activating Factor Transgenic Mice
Reduced Adult Neurogenesis and Altered Emotional Behaviors in Autoimmune-Prone B-Cell Activating Factor Transgenic Mice
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DOI：
10.1016/j.biopsych.2009.12.008
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发表时间：
2010-03-15
影响因子：
10.6
通讯作者：
Battaglia, Fortunato
中科院分区：
文献类型：
--
作者：
Crupi, Rosalia;Cambiaghi, Marco;Battaglia, Fortunato
背景资料：据推测，与自身免疫性疾病相关的脑炎症过程可能是情绪障碍的致病因素。因此，我们研究了情绪行为的自身免疫倾向的细胞因子B细胞激活因子（BAFF）转基因小鼠，系统性红斑狼疮，类风湿性关节炎，和Sjogren's syndrome.Methods的模型：男性BAFF转基因小鼠进行了一系列的标准实验室测定的情绪。小鼠脑炎症，应激诱导的c-Fos表达，海马祖细胞增殖，海马神经发生依赖和神经发生独立的长时程增强（LTP）。结果：我们的研究表明，老年BAFF转基因小鼠表现出焦虑样表型与脑炎症。此外，焦虑的小鼠在边缘系统内显示出异常的神经元激活，以响应轻度的焦虑刺激。在焦虑的BAFF转基因小鼠中，成年海马颗粒下区新形成的神经元的增殖显着减少，这些小鼠也表现出神经发生依赖性和神经发生非依赖性齿状回LTP受损。我们的研究结果表明，与系统性红斑狼疮、类风湿性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脑部炎症、神经发生受损、和海马可塑性。BAFF转基因小鼠可用于未来的研究，以测试用于治疗与自身免疫性疾病相关的情绪障碍的治疗价值的化合物。
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 Sjogren'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 Sjogren'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.