Autoresuscitation responses to hypoxia-induced apnea are delayed in newborn 5-HT-deficient Pet-1 homozygous mice.
Autoresuscitation is a critical survival-promoting mechanism in mammals that allows recovery from primary apnea via hypoxia-induced gasping. Here we show, using head-out plethysmography, that gasping behavior is altered during autoresuscitation, and the autoresuscitation response is delayed, in neonatal 5-hydroxytryptamine (5-HT) neuron-deficient Pet-1 homozygous (Pet-1(-/-)) mice. When exposed to 97% N(2)-3% CO(2) on postnatal day 4.5, unanesthetized Pet-1(-/-) mice required over four times longer than age-matched wild-type controls to initiate gasping following primary apnea. When oxygen was made available before the first gasp, allowing autoresuscitation to occur, gasping frequency was decreased and the duration of the gasping period was extended in the Pet-1 mutants compared with wild type, resulting in a nearly threefold increase in the time needed for successful autoresuscitation. However, when the exposure to anoxia was unrelenting, gasping frequency, the form of the gasps, the total number of gasps produced, the duration of the gasping period, and time to last gasp were comparable to controls. Plethysmographic testing of the same mutants on postnatal day 9.5 revealed that their autoresuscitation responses, although improved compared with day 4.5, remained significantly longer than in wild-type controls. Our data indicate that despite a severe deficiency of central 5-HT neurons, Pet-1(-/-) neonatal mice are capable of gasping, but their gasping pattern is altered during autoresuscitation, leading to a prolongation of the time required to recover from hypoxia-induced apnea.
Erickson
Jeffery T
JT
Biology Department, The College of New Jersey, Ewing, NJ 08628, USA. erickson@tcnj.edu
Sposato
Brian C
BC
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001049:Apnea / Q000209:etiology* / Q000503:physiopathology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D006720:Homozygote; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010991:Plethysmography / Q000379:methods; D020127:Recovery of Function; D012151:Resuscitation; D012701:Serotonin / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
D012701:Serotonin