title: Eliminating medullary 5-HT neurons delays arousal and decreases the respiratory response to repeated episodes of hypoxia in neonatal rat pups.
abstract: Arousal from sleep is a critical defense mechanism when infants are exposed to hypoxia, and an arousal deficit has been postulated as contributing to the etiology of the sudden infant death syndrome (SIDS). The brainstems of SIDS infants are deficient in serotonin (5-HT) and tryptophan hydroxylase (TPH) and have decreased binding to 5-HT receptors. This study explores a possible connection between medullary 5-HT neuronal activity and arousal from sleep in response to hypoxia. Medullary raphe 5-HT neurons were eliminated from neonatal rat pups with intracisterna magna (CM) injections of 5,7-dihydroxytryptamine (DHT) at P2-P3. Each pup was then exposed to four episodes of hypoxia during sleep at three developmental ages (P5, P15, and P25) to produce an arousal response. Arousal, heart rate, and respiratory rate responses of DHT-injected pups were compared with pups that received CM artificial cerebrospinal fluid (aCSF) and those that received DHT but did not have a significant reduction in medullary 5-HT neurons. During each hypoxia exposure, the time to arousal from the onset of hypoxia (latency) was measured together with continuous measurements of heart and respiratory rates, oxyhemoglobin saturation, and chamber oxygen concentration. DHT-injected pups with significant losses of medullary 5-HT neurons exhibited significantly longer arousal latencies and decreased respiratory rate responses to hypoxia compared with controls. These results support the hypothesis that in newborn and young rat pups, 5-HT neurons located in the medullary raphe contribute to the arousal response to hypoxia. Thus alterations medullary 5-HT mechanisms might contribute to an arousal deficit and contribute to death in SIDS infants.
authors.affiliation: Department of Physiology and Neurobiology and Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; robert.a.darnall@hitchcock.org.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Darnall
authors.affiliation: Department of Physiology and Neurobiology and.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schneider
authors.affiliation: Department of Physiology and Neurobiology and.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Tobia
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, and Department of Anesthesia, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Commons
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D056152:Respiratory Rate / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D010100:Oxygen
keywords: arousal; medulla; response to hypoxia; rodent development; serotonin