Oxygen sensing neurons and neuropeptides regulate survival after anoxia in developing C. elegans

John J. Flibotte, Angela M. Jablonski, Robert G. Kalb

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals.

Original languageEnglish (US)
Article numbere101102
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 26 2014

Funding

We are indebted to Dr. Manuel Zimmer for the gift of oxygen sensing worm strains used in this work, for helpful suggestions and background information, and for critical review of the manuscript. Additionally, Drs. Maria Lim and Saima Aftab provided helpful suggestions in the design of experiments. Drs. Harry Ischiropoulos and Kevin Dysart also provided helpful comments on the manuscript. Some strains used in this work were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

ASJC Scopus subject areas

  • General
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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