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Microbial colonization is required for normal neurobehavioral development in zebrafish.
Citation:
Phelps, D., N. Brinkman, S. Keely, D. Hunter, A. Gearhart, D. Betancourt, C. Wood, AND T. Tal. Microbial colonization is required for normal neurobehavioral development in zebrafish. SOT Annual Meeting, Baltimore, MD, March 12 - 16, 2017.
Impact/Purpose:
This study describes a method to generate sterile and colonized zebrafish. The work shows that there is a developmental requirement for microbes in order to stimulate normal locomotor activity, a readout of brain function.
Description:
Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we explored differences in swimming behavior between sterile (axenic), conventionalized (sterile zebrafish colonized with bacteria at 1 day post fertilization (dpf)) and conventionally raised zebrafish larvae using a standard locomotor assay consisting of alternating light and dark periods. 16S ribosomal DNA sequencing confirmed sterility in axenic zebrafish and showed that conventionalized or conventionally raised zebrafish display diverse bacterial communities dominated by Bacteriodetes and Proteobacteria phyla. At 10 dpf, axenic zebrafish display significant hyperactivity as compared to conventionalized controls. Conventionally raised zebrafish exposed to the antibiotics amphotericin B, kanamycin, and ampicillin during development also exhibited hyperactivity at 10 dpf. To determine whether there is a developmental requirement for microbial colonization, axenic embryos were conventionalized on 1, 3, 6, or 9 dpf. Hyperactivity was blocked in larvae conventionalized on 1, 3, or 6 dpf, but not on 9 dpf. To determine whether these data coincide with microbial colonization of the gut, axenic embryos were colonized with a fluorescent strain of bacteria (A. veronii:dTomato) at 1 dpf. Colonization commenced upon hatching from the chorion and reached the full extent of the gut by 4 dpf. These data show that microbial colonization is required for normal neurobehavioral development and raise the intriguing possibility that neurobehavioral toxicants might also act through a mechanism related to altered bacterial colonization of the gut during development. This abstract does not necessarily reflect EPA policy.