Toxocara canis - and Toxocara cati -Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations

• Published in: Microorganisms (Basel) 2022-01, Vol.10 (1), p.177
• Main Authors: Waindok, Patrick, Janecek-Erfurth, Elisabeth, Lindenwald, Dimitri L, Wilk, Esther, Schughart, Klaus, Geffers, Robert, Strube, Christina
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid; Apoptosis; Axon guidance; Biosynthesis; Brain; Central nervous system; Cerebellum; Cholesterol; cholesterol biosynthesis; Dementia disorders; differential transcription; DNA microarrays; Drinking water; Gene expression; gene transcription analysis; Genomes; Host-parasite interactions; Infections; Invasiveness; Laboratory animals; Larvae; Lipids; Nematodes; neural larva migrans; Neurodegenerative diseases; Parasites; Pathogenesis; Principal components analysis; Robo protein; Secretase; Slit protein; Statistical analysis; Toxocara; Toxocara canis; Toxocara cati; toxocariasis; toxocarosis; Transcription; Transcriptomics; Veterinary medicine
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms10010177

and are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of 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 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 evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In -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 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.