Prenatal intermittent hypoxia sensitizes the laryngeal chemoreflex, blocks serotoninergic shortening of the reflex, and reduces 5-HT3 receptor binding in the NTS in anesthetized rat pups

• Published in: Experimental neurology Vol. 326; p. 113166
• Main Authors: Donnelly, William T., Haynes, Robin L., Commons, Kathryn G., Erickson, Drexel J., Panzini, Chris M., Xia, Luxi, Han, Q. Joyce, Leiter, J.C.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2020
• Subjects: 5-HT3 receptor; Autonomic neuroscience; Autoradiography; Intermittent hypoxia; Laryngeal chemoreflex; Serotonin; SIDS; SIDS; Serotonin; FIO2; ECG; Autonomic neuroscience; TRPV1; NTS; RA; Intermittent hypoxia; P; Autoradiography; ANOVA; GABA; LCR; SUID; 5-HT; Laryngeal chemoreflex; EMG; 5-HT3 receptor; IH
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2019.113166

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-HT3 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-HT3 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. •We tested the hypothesis that intermittent intrauterine hypoxia (IH) would prolong laryngeal chemoreflex (LCR) apnea•Prenatal exposure to IH was associated with prolongation of the LCR in younger, postnatal (P) rat pups age P8 to P16, but not older pups•Serotonin (5-HT) Microinjected serotonin in the nucleus of the solitary tract shortened the LCR in pups exposed to room air, but not in pups exposed to prenatal IH.•The 5-HT3 receptor binding in the nucleus of the solitary tract was reduced in IH-exposed pups age P8 to P12, but not in RA-exposed ups of the same age•Prenatal IH sensitized the LCR, reduce 5-HT3 receptor binding and blunted serotonergically-mediated termination of the LCR.