A SIDS-Like Phenotype is Associated With Reduced Respiratory Chemoresponses in PACAP Deficient Neonatal Mice

  • Kevin J. Cummings
  • Jonathan D. Pendlebury
  • Frank R. Jirik
  • Nancy M. Sherwood
  • Richard J. A. Wlison
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 551)


Pituitary adenylate cyclase-activating polypeptide (PACAP) is an abundant neuropep-tide within the CNS1. Mice deficient in PACAP or the PACAP-preferring receptor (PAC1), though normal at birth, are more susceptible than littermates to death during the neonatal period2,3, with death sometimes occurring suddenly4. The reason why PACAP signaling increases the chance of surviving the neonatal period is unknown, but previous studies have indicated it is important for a proper physiological response to hypothermia5.


Neonatal Mortality Sudden Infant Death Syndrome Case Fatty Acid Oxidation Disorder Sudden Infant Death Syndrome Victim Dorsal Vagal Nucleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    N.M. Sherwood, S.L. Krueckl, and J.E. McRory, The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily, Endocr Rev 21(6) 619–70 (2000).CrossRefPubMedGoogle Scholar
  2. 2.
    H. Hashimoto, N. Shintani, K. Tanaka, W. Mori, M. Hirose, T. Matsuda, M. Sakaue, J. Miyazaki, H. Niwa, F. Tashiro, K. Yamamoto, K. Koga, S. Tomimoto, A. Kunugi, S. Suetake, and A. Baba, Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP), Proc Natl Acad Sci USA 98(23) 13355–60 (2001).CrossRefPubMedGoogle Scholar
  3. 3.
    C. Hamelink, O. Tjurmina, R. Damadzic, W.S. Young, E. Weihe, H.W. Lee, and L.E. Eiden, Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis, Proc Natl Acad Sci USA 99(1) 461–6 (2002).CrossRefPubMedGoogle Scholar
  4. 4.
    S.L. Gray, K.J. Cummings, F.R. Jirik, and N.M. Sherwood, Targeted disruption of the pituitary adenylate cyclase-activating polypeptide gene results in early postnatal death associated with dysfunction of lipid and carbohydrate metabolism, Mol Endocrinol 15(10) 1739–47 (2001).CrossRefPubMedGoogle Scholar
  5. 5.
    S.L. Gray, N. Yamaguchi, P. Vencova, and N.M. Sherwood, Temperature-sensitive phenotype in mice lacking pituitary adenylate cyclase-activating polypeptide, Endocrinology 143(10) 3946–54 (2002).CrossRefPubMedGoogle Scholar
  6. 6.
    K.J. Cummings, J.D. Pendlebury, N.M. Sherwood and R.J.A. Wilson, Sudden neonatal death in PACAP deficient mice is associated with reduced respiratory chemoresponse and susceptibility to apnea, J. Physiol: in press.Google Scholar
  7. 7.
    J.P. Mortola and C. Lanthier, The ventilatory and metabolic response to hypercapnia in newborn mammalian species, Respir Physiol 103(3) 263–70 (1996).CrossRefPubMedGoogle Scholar
  8. 8.
    J. Hannibal, Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohis-tochemical and in situ hybridization study, J. Comp Neurol 453(4) 389–417 (2002).CrossRefPubMedGoogle Scholar
  9. 9.
    M.J. Ackerman, B.L. Siu, W.Q. Sturner, D.J. Tester, C.R. Valdivia, J.C. Makielski, and J.A. Towbin, Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome, Jama 286(18) 2264–9 (2001).CrossRefPubMedGoogle Scholar
  10. 10.
    J.J. Filiano, Arcuate nucleus hypoplasia in sudden infant death syndrome: a review, Biol Neonate 65(3–4) 156–9 (1994).PubMedGoogle Scholar
  11. 11.
    C.E. Hunt, Abnormal hypercarbic and hypoxic sleep arousal responses in Near-Miss SIDS infants, PediatrRes 15(11) 1462–4 (1981).Google Scholar
  12. 12.
    K. McCulloch, R.T. Brouillette, A.J. Guzzetta, and C.E. Hunt, Arousal responses in near-miss sudden infant death syndrome and in normal infants, J Pediatr 101(6) 911–7 (1982).CrossRefPubMedGoogle Scholar
  13. 13.
    D.H. Kelly, J. Twanmoh, and D.C. Shannon, Incidence of apnea in siblings of sudden infant death syndrome victims studied at home, Pediatrics 70(1) 128–31 (1982).PubMedGoogle Scholar
  14. 14.
    W.G. Guntheroth and PS. Spiers, The triple risk hypotheses in sudden infant death syndrome, Pediatrics 110(5) e64 (2002).CrossRefPubMedGoogle Scholar
  15. 15.
    F. Guillemot, L.C. Lo, J.E. Johnson, A. Auerbach, D. J. Anderson, and A.L. Joyner, Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons, Cell 75(3) 463–76 (1993).CrossRefPubMedGoogle Scholar
  16. 16.
    E. Hummler, P. Barker, J. Gatzy, F. Beermann, C. Verdumo, A. Schmidt, R. Boucher, and B.C. Rossier, Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice, Nat Genet 12(3) 325–8 (1996).CrossRefPubMedGoogle Scholar
  17. 17.
    K. Tokieda, J.A. Whitsett, J.C. Clark, T.E. Weaver, K. Ikeda, K.B. McConnell, A.H. Jobe, M. Ikegami, and H.S. Iwamoto, Pulmonary dysfunction in neonatal SP-B-deficient mice, Am J Physiol 273(4 Pt 1) L875–82 (1997).PubMedGoogle Scholar
  18. 18.
    R.G. Boles, E.A. Buck, M.G. Blitzer, M.S. Platt, T.M. Cowan, S.K. Martin, H. Yoon, J.A. Madsen, M. Reyes-Mugica, and P. Rinaldo, Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life, J Pediatr 132(6) 924–33 (1998).CrossRefPubMedGoogle Scholar
  19. 19.
    N. Oyen, R. Skjaerven, R.E. Little, and A.J. Wilcox, Fetal growth retardation in sudden infant death syndrome (SIDS) babies and their siblings, Am J Epidemiol 142(1) 84–90 (1995).PubMedGoogle Scholar
  20. 20.
    E.A. Mitchell, P.G. Tuohy, J.M. Brunt, J.M. Thompson, M.S. Clements, A.W. Stewart, R.P. Ford, and B.J. Taylor, Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study, Pediatrics 100(5) 835–40 (1997).CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2004

Authors and Affiliations

  • Kevin J. Cummings
    • 1
  • Jonathan D. Pendlebury
    • 1
  • Frank R. Jirik
    • 2
  • Nancy M. Sherwood
    • 3
  • Richard J. A. Wlison
    • 1
  1. 1.Faculty of Medicine, Department of Physiology and BiophysicsUniversity of CalgaryCalgaryCanada
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of CalgaryCalgaryCanada
  3. 3.Department of BiologyUniversity of VictoriaVictoriaCanada

Personalised recommendations