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Effects of neonatal hyperoxia on the critical period of postnatal development of neurochemical expressions in brain stem respiratory-related nuclei in the rat. Physiol Rep 2018 Mar;6(5)

Date

03/09/2018

Pubmed ID

29516654

Pubmed Central ID

PMC5842315

DOI

10.14814/phy2.13627

Scopus ID

2-s2.0-85043577285 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

We have identified a critical period of respiratory development in rats at postnatal days P12-13, when inhibitory influence dominates and when the response to hypoxia is at its weakest. This critical period has significant implications for Sudden Infant Death Syndrome (SIDS), the cause of which remains elusive. One of the known risk factors for SIDS is prematurity. A common intervention used in premature infants is hyperoxic therapy, which, if prolonged, can alter the ventilatory response to hypoxia and induce sustained inhibition of lung alveolar growth and pulmonary remodeling. The goal of this study was to test our hypothesis that neonatal hyperoxia from postnatal day (P) 0 to P10 in rat pups perturbs the critical period by altering the normal progression of neurochemical development in brain stem respiratory-related nuclei. An in-depth, semiquantitative immunohistochemical study was undertaken at P10 (immediately after hyperoxia and before the critical period), P12 (during the critical period), P14 (immediately after the critical period), and P17 (a week after the cessation of hyperoxia). In agreement with our previous findings, levels of cytochrome oxidase, brain-derived neurotrophic factor (BDNF), TrkB (BDNF receptor), and several serotonergic proteins (5-HT1A and 2A receptors, 5-HT synthesizing enzyme tryptophan hydroxylase [TPH], and serotonin transporter [SERT]) all fell in several brain stem respiratory-related nuclei during the critical period (P12) in control animals. However, in hyperoxic animals, these neurochemicals exhibited a significant fall at P14 instead. Thus, neonatal hyperoxia delayed but did not eliminate the critical period of postnatal development in multiple brain stem respiratory-related nuclei, with little effect on the nonrespiratory cuneate nucleus.

Author List

Mu L, Xia DD, Michalkiewicz T, Hodges M, Mouradian G, Konduri GG, Wong-Riley MTT

Authors

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain Stem
Brain-Derived Neurotrophic Factor
Electron Transport Complex IV
Female
Hyperoxia
Male
Oxygen Inhalation Therapy
Rats
Rats, Sprague-Dawley
Receptor, trkB
Receptors, Serotonin
Respiration
Serotonin Plasma Membrane Transport Proteins
Tryptophan Hydroxylase