Enhanced expressions of neurodegeneration-associated factors, UPS impairment, and excess Aβ accumulation in the hippocampus of mice with persistent cerebral toxocariasis

Abstract

BackgroundToxocariasis is a worldwide zoonotic parasitic disease mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ovum-contaminated food, water, or encapsulated larvae in paratenic hosts’ viscera or meat. Since humans and mice are paratenic hosts of T. canis, the wandering larvae might cause mechanical tissue damage and excretory-secretory antigens may trigger inflammatory injuries to local organs. Long-term residence of T. canis larvae in a paratenic host’s brain may cause cerebral toxocariasis (CT) that contributes to cerebral damage, neuroinflammation and neuropsychiatric disorders in mice and clinical patients. Since the hippocampus has been long recognized as being responsible for learning and memory functions, parasitic invasion of this site may cause neuroinflammatory and neurodegenerative disorders. The present study intended to assess pathological changes, expressions of neurodegeneration-associated factors (NDAFs), including transforming growth factor (TGF)-β1, S100B, glial fibrillary acidic protein (GFAP), transglutaminase type 2 (TG2), claudin-5, substance P (SP) and interleukin (IL)-1β, and the ubiquitin-proteasome system (UPS) function in the hippocampus and associated cognitive behavior in ICR mice orally inoculated with a high, medium or low-dose of T. canis embryonated ova during a 20-week investigation.ResultsResults indicated although there were insignificant differences in learning and memory function between the experimental mice and uninfected control mice, possibly because the site where T. canis larvae invaded was the surrounding area but not the hippocampus per se. Nevertheless, enhanced expressions of NDAF, persistent UPS impairment and excess amyloid β (Aβ) accumulation concomitantly emerged in the experimental mice hippocampus at 8, 16 and 20 weeks post-infection.ConclusionsWe thus postulate that progressive CT may still progress to neurodegeneration due to enhanced NDAF expressions, persistent UPS impairment and excess Aβ accumulation in the hippocampus.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2578-6) contains supplementary material, which is available to authorized users.

Seropositivity for toxocariasis is associated with worse cognitive functioning in older adults: The national health and nutrition examination survey 2011 to 2014

“…In addition, as part of the cerebral immune response, Toxocara infection is shown to alter in ammatory mediators, such as proin ammatory cytokines and chemokines, which may result in brain dysfunction (31). In particular, animal models demonstrated neurodegenerative changes related to cerebral Toxocara infections, such as accumulation of the amyloid beta and increased expression of the ubiquitin-proteasome system (9). Future studies are expected to clarify the underlying mechanism.…”

Identification of Toxocara canis Antigen-Interacting Partners by Yeast Two-Hybrid Assay and a Putative Mechanism of These Host–Parasite Interactions

“…MAOB regulates the expression of β-amyloid, which is a key molecule in the pathogenesis of Alzheimer’s disease [ 75 ]. MAOB may also be involved in the pathology of neurotoxocariasis, as increased levels of β-amyloid precursor protein [ 76 ] and insoluble β-amyloid accumulations were observed in the brains of mice infected with T. canis [ 77 ].…”

Infectious origin of Alzheimer’s disease: Amyloid beta as a component of brain antimicrobial immunity

“…Besides neuroinflammation [ 137 , 138 ] and neurobehavioral changes [ 139 ] observed in infected mice, 2 specific features were proposed to be of particular importance regarding AD pathology. First, it is increased production and progressive accumulation of APP, Aβ, and phosphorylated tau in mouse brains [ 140 , 141 ]. While APP localizes mostly to axons, indicating axonal injury [ 142 , 143 ], the distribution of Aβ has not been examined.…”