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Updated: Dec 18, 2025
Brain Ventricular Microinjections of Lipopolysaccharide into Larval Zebrafish to Assess Neuroinflammation and Neurotoxicity
Published on: August 23, 2022
Effects of Pseudoloma neurophilia infection on the brain transcriptome in zebrafish (Danio rerio)
Helene L E Midttun1, Marco A Vindas1, Paul J Whatmore2
1Faculty of Veterinary Medicine, Department of Paraclinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.
Abstract:
Laboratory zebrafish are commonly infected with the intracellular, brain-infecting microsporidian parasite Pseudoloma neurophilia. Chronic P. neurophilia infections induce inflammation in meninges, brain and spinal cord, and have been suggested to affect neural functions since parasite clusters reside inside neurons. However, underlying neural and immunological mechanisms associated with infection have not been explored. Utilizing RNA-sequencing analysis, we found that P. neurophilia infection upregulated 175 and downregulated 45 genes in the zebrafish brain, compared to uninfected controls. Four biological pathways were enriched by the parasite, all of which were associated with immune function. In addition, 14 gene ontology (GO) terms were enriched, eight of which were associated with immune responses and five with circadian rhythm. Surprisingly, no differentially expressed genes or enriched pathways were specific for nervous system function. Upregulated immune-related genes indicate that the host generally show a pro-inflammatory immune response to infection. On the other hand, we found a general downregulation of immune response genes associated with anti-pathogen functions, suggesting an immune evasion strategy by the parasite. The results reported here provide important information on host-parasite interaction and highlight possible pathways for complex effects of parasite infections on zebrafish phenotypes.
Insights
Zebrafish infected with Pseudoloma neurophilia show immune responses and circadian rhythm changes, but no direct neural gene expression changes. This parasite may use immune evasion strategies, impacting host phenotypes.
Area of Science:
- Neuroimmunology
- Parasitology
- Zebrafish models
Background:
- Zebrafish are susceptible to Pseudoloma neurophilia, a brain-infecting microsporidian parasite.
- Chronic infections cause inflammation and may affect neural functions due to parasite location within neurons.
Purpose of the Study:
- To investigate the neural and immunological mechanisms underlying P. neurophilia infection in zebrafish.
- To identify host gene expression changes and biological pathways affected by the parasite.
Main Methods:
- RNA-sequencing analysis of zebrafish brains from infected and uninfected control groups.
- Differential gene expression analysis and pathway enrichment analysis (Gene Ontology).
Main Results:
- P. neurophilia infection altered gene expression in zebrafish brains, upregulating 175 genes and downregulating 45.
- Enriched pathways were primarily associated with immune function and circadian rhythm, not nervous system function.
- Upregulated immune genes suggest a pro-inflammatory response, while downregulated anti-pathogen genes indicate parasite immune evasion.
Conclusions:
- Zebrafish mount an immune response to P. neurophilia, but the parasite employs strategies to evade host defenses.
- Circadian rhythm pathways are affected, alongside immune responses, suggesting complex host-parasite interactions.
- The study provides insights into host-parasite interactions and potential impacts on zebrafish phenotypes.
