Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii

Raul Chavez-Valdez, Ariel Mason, Ana R. Nunes, Frances J. Northington, Clarke Tankersley, Rajni Ahlawat, Sheree M. Johnson, Estelle B. Gauda

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% (P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% (P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% (P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.

Original languageEnglish (US)
Pages (from-to)1762-1772
Number of pages11
JournalJournal of applied physiology
Volume112
Issue number10
DOIs
StatePublished - May 15 2012

Keywords

  • Brain-derived neurotrophic factor
  • Glial-derived neurotrophic factor
  • Hypoxic ventilatory response
  • Peripheral arterial chemoreceptors
  • Plasticity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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