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Functional Recovery from Neonatal Breathing Abnormalities in 5HT‐Deficient Pet‐1 Knockout Mice Following Developmental Exposure to Nicotine
Author(s) -
Erickson Jeffery,
Delatour Laurie,
Nardone Jessica,
Stewart Amanda
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.861.4
Subject(s) - ventilation (architecture) , knockout mouse , context (archaeology) , medicine , endocrinology , 5 ht receptor , raphe , nicotine , serotonin , biology , receptor , serotonergic , mechanical engineering , paleontology , engineering
Serotonin (5HT) is known to modulate central neural circuits controlling breathing in mammals. Pet‐1 gene knockout (KO) leads to a 70% loss of central 5HT neurons and breathing deficits in neonates, including reduced breathing frequency, more spontaneous apneas, delayed autoresuscitation responses, and higher neonatal mortality compared to wild type (WT) littermates. We tested the effects of nicotine (NIC) on breathing in a 5HT‐deficient context by exposing fetuses to saline (SAL) or NIC (60 mg/kg dam body weight) from day 5 of gestation via osmotic mini‐pump implants in pregnant dams and compared resting ventilation and autoresuscitation in WT and KO neonates. Relative to WT SAL‐treated mice, Pet‐1 KO neonates suffered depressed resting ventilation, more frequent apneas, and delayed autoresuscitation responses, as expected. However, these breathing deficits were reversed in KO mice following NIC exposure despite continued high neonatal mortality in this group. Analysis of the caudal raphe nuclei showed a similar (~70%) loss of 5HT neurons in both NIC‐ and SAL‐treated KO mice compared to WT controls. We conclude that a full complement of 5HT neurons normally promotes but is not absolutely necessary for producing normal resting ventilation and autoresuscitation responses in mouse neonates, although the underlying mechanism by which NIC exposure can compensate for a 5HT neuron deficit is unclear. In addition, we speculate that the high neonatal mortality of Pet‐1 KO mice may be due to abnormal cardiac function, rather than breathing dysfunction per se. Supported by the CJ Foundation for SIDS and a TCNJ SOSA award.