Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Neuronal Apoptosis: Pathological Basis of Behavioral Dysfunctions Induced by Angiostrongylus cantonensis in Rodents Model

  • Luo, Shiqi (Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University) ;
  • OuYang, Lisi (Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University) ;
  • Wei, Jie (Department of Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University) ;
  • Wu, Feng (Department of Clinical Laboratory, the Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Wu, Zhongdao (Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University) ;
  • Lei, Wanlong (Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University) ;
  • Yuan, Dongjuan (Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University)
  • Received : 2017.05.06
  • Accepted : 2017.05.25
  • Published : 2017.06.30
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Abstract

Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.

Keywords

References

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