Prenatal Intermittent Hypoxia Sensitizes the Laryngeal Chemoreflex, Blocks Serotoninergic Shortening of the Reflex, and Reduces 5-HT Receptor Binding in the NTS in Anesthetized Rat Pups

Overview

Journal Exp Neurol

Specialty Neurology

Date 2019 Dec 31

PMID 31887303

Citations 2

Authors

William T Donnelly

Robin L Haynes

Kathryn G Commons

Drexel J Erickson

Chris M Panzini

Luxi Xia

Q Joyce Han

J C Leiter

Affiliations

Soon will be listed here.

Abstract

We tested the hypothesis that exposure to intermittent hypoxia (IH) during pregnancy would prolong the laryngeal chemoreflex (LCR) and diminish the capacity of serotonin (5-hydroxytryptamine; 5-HT) to terminate the LCR. Prenatal exposure to IH was associated with significant prolongation of the LCR in younger, anesthetized, postnatal day (P) rat pups age P8 to P16 compared to control, room air (RA)-exposed rat pups of the same age. Serotonin microinjected into the NTS shortened the LCR in rat pups exposed to RA during gestation, but 5-HT failed to shorten the LCR in rat pups exposed to prenatal IH. Given these observations, we tested the hypothesis that prenatal hypoxia would decrease binding to 5-HT receptors in the nucleus of the solitary tract (NTS) where 5-HT acts to shorten the LCR. Serotonin 3 receptor binding was reduced in younger rat pups exposed to IH compared to control, RA-exposed rat pups in the age range P8 to P12. Serotonin 3 receptor binding was similar in older animals (P18-P24) regardless of gas exposure during gestation. The failure of the 5-HT injected into the NTS to shorten the LCR was correlated with a developmental decrease in 5-HT receptor binding in the NTS associated with exposure to prenatal IH. In summary, prenatal IH sensitized reflex apnea and blunted processes that terminate reflex apneas in neonatal rat pups, processes that are essential to prevent death following apneas such as those seen in babies who died of SIDS.

Citing Articles

Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part II. Age-associated alterations in serotonin receptor binding profiles within medullary nuclei supporting cardiorespiratory homeostasis.

Cummings K, Leiter J, Trachtenberg F, Okaty B, Darnall R, Haas E J Neuropathol Exp Neurol. 2024; 83(3):144-160.

PMID: 38323418 PMC: 10880067. DOI: 10.1093/jnen/nlae004.

Prenatal cannabis use disorder and infant hospitalization and death in the first year of life.

Bandoli G, Delker E, Schumacher B, Baer R, Kelly A, Chambers C Drug Alcohol Depend. 2022; 242:109728.

PMID: 36516553 PMC: 10363398. DOI: 10.1016/j.drugalcdep.2022.109728.

References

Marty V, El Hachmane M, Amedee T . Dual modulation of synaptic transmission in the nucleus tractus solitarius by prostaglandin E2 synthesized downstream of IL-1beta. Eur J Neurosci. 2008; 27(12):3132-50. DOI: 10.1111/j.1460-9568.2008.06296.x. View

Bright F, Byard R, Vink R, Paterson D . Medullary Serotonin Neuron Abnormalities in an Australian Cohort of Sudden Infant Death Syndrome. J Neuropathol Exp Neurol. 2017; 76(10):864-873. DOI: 10.1093/jnen/nlx071. View

Broadbelt K, Paterson D, Rivera K, Trachtenberg F, Kinney H . Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla. Auton Neurosci. 2009; 154(1-2):30-41. PMC: 2844926. DOI: 10.1016/j.autneu.2009.10.002. View

Page M, Jeffery H . The role of gastro-oesophageal reflux in the aetiology of SIDS. Early Hum Dev. 2000; 59(2):127-49. DOI: 10.1016/s0378-3782(00)00093-1. View

Hermes S, Andresen M, Aicher S . Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat. J Chem Neuroanat. 2015; 72:1-7. PMC: 4764453. DOI: 10.1016/j.jchemneu.2015.12.003. View

Downing S, Lee J . Laryngeal chemosensitivity: a possible mechanism for sudden infant death. Pediatrics. 1975; 55(5):640-9. View

Malloy M . Trends in postneonatal aspiration deaths and reclassification of sudden infant death syndrome: impact of the "Back to Sleep" program. Pediatrics. 2002; 109(4):661-5. DOI: 10.1542/peds.109.4.661. View

Czyzyk-Krzeska M, Lawson E . Synaptic events in ventral respiratory neurones during apnoea induced by laryngeal nerve stimulation in neonatal pig. J Physiol. 1991; 436:131-47. PMC: 1181498. DOI: 10.1113/jphysiol.1991.sp018543. View

Poets C, Samuels M, Noyes J, Hewertson J, Hartmann H, Holder A . Home event recordings of oxygenation, breathing movements, and heart rate and rhythm in infants with recurrent life-threatening events. J Pediatr. 1993; 123(5):693-701. DOI: 10.1016/s0022-3476(05)80842-x. View

10.

STOLTENBERG L, Sundar T, Almaas R, Storm H, Rognum T, Saugstad O . Changes in apnea and autoresuscitation in piglets after intravenous and intrathecal interleukin-1 beta injection. J Perinat Med. 1994; 22(5):421-32. DOI: 10.1515/jpme.1994.22.5.421. View

11.

Xia L, Damon T, Leiter J, Bartlett Jr D . Focal warming in the nucleus of the solitary tract prolongs the laryngeal chemoreflex in decerebrate piglets. J Appl Physiol (1985). 2006; 102(1):54-62. DOI: 10.1152/japplphysiol.00720.2006. View

12.

Kinney H, Filiano J, Sleeper L, Mandell F, VALDES-DAPENA M, White W . Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome. Science. 1995; 269(5229):1446-50. DOI: 10.1126/science.7660131. View

13.

Jin Y, Bailey T, Li B, Schild J, Andresen M . Purinergic and vanilloid receptor activation releases glutamate from separate cranial afferent terminals in nucleus tractus solitarius. J Neurosci. 2004; 24(20):4709-17. PMC: 6729471. DOI: 10.1523/JNEUROSCI.0753-04.2004. View

14.

Xia L, Bartlett Jr D, Leiter J . Interleukin-1β and interleukin-6 enhance thermal prolongation of the LCR in decerebrate piglets. Respir Physiol Neurobiol. 2016; 230:44-53. PMC: 5505566. DOI: 10.1016/j.resp.2016.05.006. View

15.

Kinney H, Brody B, Finkelstein D, VAWTER G, Mandell F, Gilles F . Delayed central nervous system myelination in the sudden infant death syndrome. J Neuropathol Exp Neurol. 1991; 50(1):29-48. DOI: 10.1097/00005072-199101000-00003. View

16.

Takashima S, Becker L . Delayed dendritic development of catecholaminergic neurons in the ventrolateral medulla of children who died of sudden infant death syndrome. Neuropediatrics. 1991; 22(2):97-9. DOI: 10.1055/s-2008-1071424. View

17.

Mutoh T, Kanamaru A, Kojima K, Nishimura R, Sasaki N, Tsubone H . Effects of perineural capsaicin treatment on cardiopulmonary reflexes elicited by laryngeal instillations of capsaicin and distilled water in sevoflurane-anesthetized dogs. J Vet Med Sci. 2000; 62(6):665-8. DOI: 10.1292/jvms.62.665. View

18.

Meny R, Carroll J, Carbone M, Kelly D . Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home. Pediatrics. 1994; 93(1):44-9. View

19.

Kinney H, Haynes R . The Serotonin Brainstem Hypothesis for the Sudden Infant Death Syndrome. J Neuropathol Exp Neurol. 2019; 78(9):765-779. PMC: 6934437. DOI: 10.1093/jnen/nlz062. View

20.

Ostfeld B, Schwartz-Soicher O, Reichman N, Teitler J, Hegyi T . Prematurity and Sudden Unexpected Infant Deaths in the United States. Pediatrics. 2017; 140(1). DOI: 10.1542/peds.2016-3334. View