Janecek Elisabeth, Waindok Patrick, Bankstahl Marion, Strube Christina
Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hanover, Germany.
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hanover, Germany.
PLoS Negl Trop Dis. 2017 May 8;11(5):e0005594. doi: 10.1371/journal.pntd.0005594. eCollection 2017 May.
Neuroinvasive larvae of the worldwide occurring zoonotic roundworms Toxocara canis and T. cati may induce neurotoxocarosis (NT) in humans, provoking a variety of symptoms including cognitive deficits as well as neurological dysfunctions. An association with neuropsychological disorders has been discussed. Similar symptoms have been described in T. canis-infected mice, whereas data on T. cati-induced NT are rare. Therefore, it was aimed to obtain insights into the impact on neurobehaviour as well as progression of neurological symptoms and behavioural alterations during the course of NT directly comparing T. canis- and T. cati-infected mice as models for human NT.
METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice were orally infected with 2000 embryonated T. canis or T. cati eggs, respectively, the control group received tap water. Mice were screened weekly for neurobehavioural alterations and memory function starting one day prior infection until 97 days post infection (pi; T. canis-infection) and day 118 pi (T. cati-infection, uninfected control). Mostly motoric and neurological parameters were affected in T. canis-infected mice starting day 20 pi with severe progression accompanied by stereotypical circling. In contrast, T. cati-infected mice mostly showed reduced response to sudden sound stimulus (indicator for excitability) and flight behaviour starting day 6 pi. Interestingly, enhanced grooming behaviour was observed exclusively in T. cati-infected mice, indicating a possible role of neurotransmitter dysregulation. Reduced exploratory behaviour and memory impairment was observed in both infection groups with delayed onset and less severe progression in T. cati- compared to T. canis-infected mice.
CONCLUSIONS/SIGNIFICANCE: Results highlight the need to consider T. cati beside T. canis as causative agent of human NT. Findings provide valuable hints towards differences in key regulatory mechanisms during T. canis- and T. cati-induced NT, contributing to a comprehensive picture and consequently a broader understanding of NT, which will aid in developing strategies towards prevention in addition to novel diagnostic and therapeutic approaches.
全球广泛存在的人兽共患蛔虫犬弓首线虫和猫弓首线虫的神经侵袭性幼虫可在人类中诱发神经弓首线虫病（NT），引发包括认知缺陷以及神经功能障碍在内的多种症状。人们已讨论过其与神经心理障碍的关联。在感染犬弓首线虫的小鼠中也描述过类似症状，而关于猫弓首线虫诱发NT的数据却很少。因此，旨在通过直接比较感染犬弓首线虫和猫弓首线虫的小鼠作为人类NT模型，深入了解NT病程中对神经行为的影响以及神经症状和行为改变的进展情况。
方法/主要发现：将C57BL/6小鼠分别经口感染2000枚感染性犬弓首线虫或猫弓首线虫卵，对照组给予自来水。从感染前一天开始至感染后97天（犬弓首线虫感染组）和感染后118天（猫弓首线虫感染组、未感染对照组），每周对小鼠进行神经行为改变和记忆功能筛查。感染犬弓首线虫的小鼠从感染后第20天开始，大多数运动和神经参数受到影响，病情严重进展并伴有刻板的转圈行为。相比之下，感染猫弓首线虫的小鼠从感染后第6天开始，大多表现出对突发声音刺激的反应降低（兴奋性指标）和逃避行为。有趣的是，仅在感染猫弓首线虫的小鼠中观察到梳理行为增强，这表明神经递质失调可能起作用。在两个感染组中均观察到探索行为减少和记忆障碍，与感染犬弓首线虫的小鼠相比，感染猫弓首线虫的小鼠发病延迟且病情进展较轻。
结论/意义：结果凸显了除犬弓首线虫外，还需将猫弓首线虫视为人类NT病原体的必要性。研究结果为犬弓首线虫和猫弓首线虫诱发NT期间关键调节机制的差异提供了有价值的线索，有助于形成全面认识，从而更广泛地理解NT，这将有助于制定预防策略以及开发新的诊断和治疗方法。
