Bowles Center for Alcohol Studies, USA.
Bowles Center for Alcohol Studies, USA; Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Behav Brain Res. 2023 Feb 13;438:114200. doi: 10.1016/j.bbr.2022.114200. Epub 2022 Nov 2.
There are many unanswered questions about the interaction between the immune system and behavior change, including the contributions of individual differences. The present study modeled individual differences in the immune system by comparing inbred Lewis rats, which have dysregulated stress and immune systems, to their genetically diverse parent strain, Wistar rats. The objective was to examine the consequences of an immune challenge on behavior and neuroimmune signaling in both strains. Peripheral administration of the toll-like receptor 3 (TLR3) agonist and viral memetic polyinosinic-polycytidylic acid (poly(I:C)) induced behavior changes in both strains, reducing locomotor activity and increasing avoidance behavior (time on the dark side of the light-dark box). Furthermore, poly(I:C) induced hyperarousal and increased avoidance behavior more in female Lewis than female Wistar rats. Baseline strain differences were also observed: Lewis rats had higher avoidance behavior and lower startle response than Wistars. Lewis rats also had lower levels of peripheral inflammation, as measured by spleen weight. Finally, poly(I:C) increased expression of genes in the TLR3 pathway, cytokine genes, and CD11b, a gene associated with proinflammatory actions of microglia, in the prelimbic cortex and central amygdala, with greater expression of cytokine genes in male rats. Lewis rats had lower baseline expression of some neuroimmune genes, particularly CD11b. Overall, we found constitutive strain differences in immune profiles and baseline differences in behavior, yet poly(I:C) generally induced similar behavior changes in males while hyperarousal and avoidance behavior were heightened in female Lewis rats.
关于免疫系统与行为改变之间的相互作用，存在许多尚未解答的问题，包括个体差异的贡献。本研究通过比较具有失调的应激和免疫系统的近交系 Lewis 大鼠与其遗传多样化的亲本品系 Wistar 大鼠，来模拟免疫系统的个体差异。目的是研究免疫挑战对两种品系的行为和神经免疫信号的影响。外周给予 Toll 样受体 3（TLR3）激动剂和病毒模拟物聚肌胞苷酸（poly(I:C)）可引起两种品系的行为改变，减少运动活动并增加回避行为（在明暗箱的黑暗侧上的时间）。此外，poly(I:C) 在雌性 Lewis 大鼠中比在雌性 Wistar 大鼠中诱导更强的觉醒和更多的回避行为。还观察到基线品系差异：Lewis 大鼠的回避行为高于 Wistar 大鼠，而惊吓反应低于 Wistar 大鼠。Lewis 大鼠的外周炎症水平也较低，以脾脏重量衡量。最后，poly(I:C) 增加了 TLR3 途径、细胞因子基因和与小胶质细胞促炎作用相关的基因 CD11b 在额前皮质和中央杏仁核中的表达，雄性大鼠的细胞因子基因表达更高。Lewis 大鼠的一些神经免疫基因的基础表达较低，尤其是 CD11b。总体而言，我们发现免疫谱存在固有的品系差异，行为存在基线差异，但 poly(I:C) 通常在雄性中诱导类似的行为改变，而雌性 Lewis 大鼠的觉醒和回避行为增强。
