<i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
<i>Toxocara canis</i> and <i>Toxocara cati</i> are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of <i>Toxocara</i> larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxoc...
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MDPI AG
2022-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/1/177 |
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| author | Patrick Waindok Elisabeth Janecek-Erfurth Dimitri L. Lindenwald Esther Wilk Klaus Schughart Robert Geffers Christina Strube |
| author_facet | Patrick Waindok Elisabeth Janecek-Erfurth Dimitri L. Lindenwald Esther Wilk Klaus Schughart Robert Geffers Christina Strube |
| author_sort | Patrick Waindok |
| collection | DOAJ |
| description | <i>Toxocara canis</i> and <i>Toxocara cati</i> are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of <i>Toxocara</i> larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses against <i>Toxocara</i> larvae are mostly unknown, whole-genome microarray transcription analysis was performed in cerebra and cerebella of experimentally infected C57Bl/6J mice as paratenic host model at days 14, 28, 70, 98, and 120 post-infection. Neuroinvasion of <i>T. cati</i> evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In <i>T. canis</i>-infected mice, 1039 cerebral and 2073 cerebellar DTGs were identified. Statistically significant dysregulations occurred in various pathways, including cholesterol biosynthesis, apoptosis signaling, and the Slit/Robo mediated axon guidance as well as different pathways associated with the immune and defense response. Observed dysregulations of the cholesterol biosynthesis, as well as the Alzheimer disease-amyloid secretase pathway in conjunction with previous histopathological neurodegenerative findings, may promote the discussion of <i>T. canis</i> as a causative agent for dementia and/or Alzheimer’s disease. Furthermore, results contribute to a deeper understanding of the largely unknown pathogenesis and host-parasite interactions during NT, and may provide the basis for prospective investigations evaluating pathogenic mechanisms or designing novel diagnostic and therapeutic approaches. |
| first_indexed | 2024-03-10T00:52:54Z |
| format | Article |
| id | doaj.art-691404c78fba47a197a07b032168ec6b |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T00:52:54Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-691404c78fba47a197a07b032168ec6b2023-11-23T14:48:29ZengMDPI AGMicroorganisms2076-26072022-01-0110117710.3390/microorganisms10010177<i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic AlterationsPatrick Waindok0Elisabeth Janecek-Erfurth1Dimitri L. Lindenwald2Esther Wilk3Klaus Schughart4Robert Geffers5Christina Strube6Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, 30559 Hanover, GermanyInstitute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, 30559 Hanover, GermanyInstitute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, 30559 Hanover, GermanyDepartment of Infection Genetics, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Infection Genetics, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyResearch Group Genome Analytics, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyInstitute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, 30559 Hanover, Germany<i>Toxocara canis</i> and <i>Toxocara cati</i> are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of <i>Toxocara</i> larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses against <i>Toxocara</i> larvae are mostly unknown, whole-genome microarray transcription analysis was performed in cerebra and cerebella of experimentally infected C57Bl/6J mice as paratenic host model at days 14, 28, 70, 98, and 120 post-infection. Neuroinvasion of <i>T. cati</i> evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In <i>T. canis</i>-infected mice, 1039 cerebral and 2073 cerebellar DTGs were identified. Statistically significant dysregulations occurred in various pathways, including cholesterol biosynthesis, apoptosis signaling, and the Slit/Robo mediated axon guidance as well as different pathways associated with the immune and defense response. Observed dysregulations of the cholesterol biosynthesis, as well as the Alzheimer disease-amyloid secretase pathway in conjunction with previous histopathological neurodegenerative findings, may promote the discussion of <i>T. canis</i> as a causative agent for dementia and/or Alzheimer’s disease. Furthermore, results contribute to a deeper understanding of the largely unknown pathogenesis and host-parasite interactions during NT, and may provide the basis for prospective investigations evaluating pathogenic mechanisms or designing novel diagnostic and therapeutic approaches.https://www.mdpi.com/2076-2607/10/1/177neural larva migranstoxocarosistoxocariasisgene transcription analysisdifferential transcriptioncholesterol biosynthesis |
| spellingShingle | Patrick Waindok Elisabeth Janecek-Erfurth Dimitri L. Lindenwald Esther Wilk Klaus Schughart Robert Geffers Christina Strube <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations Microorganisms neural larva migrans toxocarosis toxocariasis gene transcription analysis differential transcription cholesterol biosynthesis |
| title | <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations |
| title_full | <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations |
| title_fullStr | <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations |
| title_full_unstemmed | <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations |
| title_short | <i>Toxocara canis</i>- and <i>Toxocara cati</i>-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations |
| title_sort | i toxocara canis i and i toxocara cati i induced neurotoxocarosis is associated with comprehensive brain transcriptomic alterations |
| topic | neural larva migrans toxocarosis toxocariasis gene transcription analysis differential transcription cholesterol biosynthesis |
| url | https://www.mdpi.com/2076-2607/10/1/177 |
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