Korean J Parasitol.  2017 Jun;55(3):267-278. 10.3347/kjp.2017.55.3.267.

Neuronal Apoptosis: Pathological Basis of Behavioral Dysfunctions Induced by Angiostrongylus cantonensis in Rodents Model

• Luo S
• OuYang L
• Wei J
• Wu F
• Wu Z
• Lei W
• Yuan D

• KMID: 2387182
• DOI: http://doi.org/10.3347/kjp.2017.55.3.267

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.

Keyword

Angiostrongylus cantonensis; eosinophilic meningitis; meningoencephalitis; apoptosis

MeSH Terms

Angiostrongylus cantonensis*
Angiostrongylus*
Animals
Apoptosis*
Behavior Rating Scale
Caspase 3
Caspase 8
Central Nervous System
Cerebral Cortex
Diagnosis
Eosinophils
Gait
Gene Expression
Headache
Hippocampus
Humans
Meningitis
Meningoencephalitis
Mice
Neurons*
Rats
Receptors, Tumor Necrosis Factor, Type I
Rodentia*
Caspase 3
Caspase 8
Receptors, Tumor Necrosis Factor, Type I