Department of Psychology and Neuroscience, Baylor University, Waco, Texas, USA.
Institute of Biomedical Studies, Baylor University, Waco, Texas, USA.
Brain Behav. 2023 Aug;13(8):e3142. doi: 10.1002/brb3.3142. Epub 2023 Jul 5.
Fragile X syndrome is the main monogenetic cause of intellectual disability and autism. Alterations in the immune system are commonly found in these developmental disorders. We and others have demonstrated that Fmr1 mutant mice present an altered response to immune stimuli. However, whether this altered immune response can influence the Fmr1 mutant behavioral outcomes in response to inflammation has not been fully investigated.
In the current study, we examine the behavioral sickness response of male wildtype and knockout mice to the innate immune stimulus lipopolysaccharide (LPS) (0.1 mg/kg) to determine if Fmr1 mutants have altered sickness behavior. We used an enzyme-linked immunosorbent assay (ELISA) to measure changes in the cytokine interleukin-6 (IL-6) to determine that inflammation was induced in the mice. Sickness behavior was assessed in a wheel-running paradigm, and a tail suspension test was used to assess the depressive-like phenotype that follows sickness behavior in response to LPS.
The ELISA using blood serum confirmed a significant increase in IL-6 in mice that were treated with LPS. Treated Fmr1 mutants exhibited decreased distance traveled in the wheel running after LPS administration, similar to treated controls. Another cohort of animals treated with LPS were tested in the tail suspension test and exhibited no alterations in immobility time in response to LPS.
Together, our data suggest that Fmr1 mutant mice do not have altered sickness behavior in response to a low dose of LPS.
脆性 X 综合征是智力障碍和自闭症的主要单基因病因。免疫系统的改变在这些发育障碍中很常见。我们和其他人已经证明，Fmr1 突变小鼠对免疫刺激的反应发生改变。然而，这种改变的免疫反应是否会影响 Fmr1 突变体对炎症的行为反应尚未得到充分研究。
在本研究中，我们检查了雄性野生型和敲除小鼠对先天免疫刺激物脂多糖（LPS）（0.1mg/kg）的行为病态反应，以确定 Fmr1 突变体是否具有改变的病态行为。我们使用酶联免疫吸附测定（ELISA）测量细胞因子白细胞介素-6（IL-6）的变化，以确定小鼠中是否发生了炎症。病态行为通过轮跑范式进行评估，尾巴悬挂测试用于评估 LPS 引起的病态行为后的抑郁样表型。
使用血清的 ELISA 证实 LPS 处理的小鼠中 IL-6 显著增加。用 LPS 处理的 Fmr1 突变体在 LPS 给药后表现出轮跑中行进距离减少，与处理对照相似。另一组接受 LPS 治疗的动物在尾巴悬挂测试中进行了测试，对 LPS 无反应的不动时间没有改变。
总之，我们的数据表明，Fmr1 突变小鼠对低剂量 LPS 的病态行为没有改变。
