Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Warsaw, Poland.
W. Stefański Institute of Parasitology, Polish Academy of Sciences, Warsaw, Poland.
PLoS Pathog. 2022 Mar 14;18(3):e1010330. doi: 10.1371/journal.ppat.1010330. eCollection 2022 Mar.
Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.
寄生虫可能会严重影响宿主的机能,包括免疫反应和肠脑轴,最终导致宿主行为的改变。肠道蠕虫对宿主中枢神经系统(CNS)的影响仍未被探索。本研究旨在评估肠道感染细粒棘球绦虫对大鼠中枢神经系统(CNS)行为和功能的影响。3 月龄的动物被感染,在 18 个月时通过旷场(OF)、新物体识别(NOR)和水迷宫(WM)测试评估其对焦虑、探索、感觉运动技能和学习过程的影响。完成行为研究后,处死感染和未感染的大鼠,并对收集的组织进行生化分析。通过 HPLC 测定 CNS 选定结构中的神经递质、其代谢物和氨基酸的水平。此外,通过实时 PCR 评估促炎和抗炎细胞因子(TNF-α、IL-1β、IL-6 和 IL-10)的基因表达谱,以确定 CNS 对绦虫感染的免疫反应。寄生虫导致了探索性行为的显著变化,尤其是在 OF 测试中,速度和总距离的降低;感染的大鼠中央区域的频率降低,这可能表明焦虑程度更高。此外,寄生虫感染改善了空间记忆,在 WM 测试中得到评估,以及对新物体的识别。这些变化与 CNS 结构中去甲肾上腺素水平的降低以及纹状体 5-羟色胺能神经传递的变化不明显有关。细粒棘球绦虫感染还导致海马体中 IL-6 的表达显著减少。我们的研究结果为进一步研究寄生虫感染期间的大脑功能提供了新的数据,特别是与可能发挥重要作用的神经递质系统有关的寄生虫和疾病。