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Microbiota is required for normal neurobehavioral development in zebrafish.
Citation:
Phelps, D., N. Brinkman, S. Keely, E. Anneken, D. Hunter, A. Gearhart, D. Betancourt, C. Wood, AND T. Tal. Microbiota is required for normal neurobehavioral development in zebrafish. RTP Drug Metabolism Discussion Group W2017 Winter Symposium, RTP, NC, March 07, 2017.
Impact/Purpose:
This abstract represents work initiated by a PIP Stage 3 Award and describes data showing that microbes are required for normal neurobehavioral development in zebrafish.
Description:
Intestinal microbiota may mediate neurodevelopmental behavioral effects of environmental chemicals either by performing biotransformations or serving as a target of chemical exposures. To investigate the consequence of microbial disruption, we evaluated axenic (sterile), conventionally raised, or conventionalized (axenic larvae colonized at 1 day post fertilization (dpf)) zebrafish larvae using a standard locomotor assay consisting of alternating light and dark periods. At 10 days post fertilization (dpf), axenic zebrafish displayed hyperactivity compared to conventionalized controls. Impairment of host colonization using antibiotics also caused hyperactivity in conventionally raised larvae. Axenic embryos were conventionalized on 1, 3, 6, or 9 dpf to determine whether there is a developmental requirement for microbial colonization. Hyperactivity was blocked in larvae conventionalized on 1-6 dpf, but not on 9 dpf. Axenic embryos monoassociated with fluorescently labeled Aeromonas veronii at 1 dpf showed that colonization commenced upon chorionic hatching and extended throughout the gut by 4 dpf. Monoassociation with Aeromonas veronii or Vibrio cholerae was also sufficient to block locomotor hyperactivity at 10 dpf. Activation of host toll-like receptors by exposure to heat killed Esherichia coli or Salmonella typhimurium or microbial associated molecular patterns (Pam3CSK4 or Poly(I:C)) failed to block locomotor hyperactivity in axenic larvae. These data show that microbial colonization during early life is required for normal neurobehavioral development and support the concept that environmental chemicals, like antibiotics, may exert neurobehavioral effects via impairment of microbial colonization. This abstract does not necessarily reflect EPA policy.