Toxocara canis- and Toxocara cati-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 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.