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

Chia Mei Chou, Yueh Lun Lee, Chien Wei Liao, Ying Chieh Huang, Chia Kwung Fan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Toxocariasis 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. Results: Results 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. Conclusions: We 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.

Original languageEnglish
Article number620
JournalParasites and Vectors
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 22 2017

Fingerprint

Toxocariasis
Toxocara canis
Proteasome Endopeptidase Complex
Ubiquitin
Hippocampus
Larva
Ovum
Claudin-5
Learning
Inbred ICR Mouse
Parasitic Diseases
Viscera
Glial Fibrillary Acidic Protein
Zoonoses
Transforming Growth Factors
Substance P
Interleukin-1
Amyloid
Neurodegenerative Diseases
Meat

Keywords

  • Amyloid β
  • Cerebral toxocariasis
  • Hippocampus
  • Mice
  • Neurodegeneration
  • Toxocara canis
  • Ubiquitin-proteasome system
  • Zoonosis

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

@article{96ea0e7b616c4b3eae47802432a15da6,
title = "Enhanced expressions of neurodegeneration-associated factors, UPS impairment, and excess Aβ accumulation in the hippocampus of mice with persistent cerebral toxocariasis",
abstract = "Background: Toxocariasis 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. Results: Results 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. Conclusions: We 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.",
keywords = "Amyloid β, Cerebral toxocariasis, Hippocampus, Mice, Neurodegeneration, Toxocara canis, Ubiquitin-proteasome system, Zoonosis",
author = "Chou, {Chia Mei} and Lee, {Yueh Lun} and Liao, {Chien Wei} and Huang, {Ying Chieh} and Fan, {Chia Kwung}",
year = "2017",
month = "12",
day = "22",
doi = "10.1186/s13071-017-2578-6",
language = "English",
volume = "10",
journal = "Parasites and Vectors",
issn = "1756-3305",
publisher = "BioMed Central",
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TY - JOUR

T1 - Enhanced expressions of neurodegeneration-associated factors, UPS impairment, and excess Aβ accumulation in the hippocampus of mice with persistent cerebral toxocariasis

AU - Chou, Chia Mei

AU - Lee, Yueh Lun

AU - Liao, Chien Wei

AU - Huang, Ying Chieh

AU - Fan, Chia Kwung

PY - 2017/12/22

Y1 - 2017/12/22

N2 - Background: Toxocariasis 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. Results: Results 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. Conclusions: We 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.

AB - Background: Toxocariasis 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. Results: Results 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. Conclusions: We 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.

KW - Amyloid β

KW - Cerebral toxocariasis

KW - Hippocampus

KW - Mice

KW - Neurodegeneration

KW - Toxocara canis

KW - Ubiquitin-proteasome system

KW - Zoonosis

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U2 - 10.1186/s13071-017-2578-6

DO - 10.1186/s13071-017-2578-6

M3 - Article

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VL - 10

JO - Parasites and Vectors

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