title: Impaired response to hypoxia in the respiratory center is a major cause of neonatal death of the PACAP-knockout mouse.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide expressed widely in nervous tissues. PACAP-knockout ((-/-)) mice display a sudden infant death syndrome (SIDS)-like phenotype, although the underlying physiological mechanism to explain this remains unclear. Here, we report on the presence of abnormal respiratory activity in PACAP(-/-) mice under hypoxic conditions, which provides a basis for the SIDS-like phenotype. PACAP(-/-) mice display a lowered baseline respiratory activity compared with wild-type animals, and an abnormal response to hypoxia. More specifically, PACAP(-/-) mice at postnatal day 7 showed respiratory arrest in response to hypoxia. In contrast, their response to hypercapnic conditions was the same as that of wild-type mice. Histological and real-time PCR analyses indicated that the catecholaminergic system in the medulla oblongata was impaired in PACAP(-/-) mice, suggesting that endogenous PACAP affects respiratory centers in the medulla oblongata via its action on the catecholaminergic system. We propose that disruption of this system is involved in the SIDS-like phenotype of PACAP(-/-) mice. Thus, disorders of the catecholaminergic system involved with O(2) sensing could be implicated in underlying neuronal mechanisms responsible for SIDS.
authors.affiliation: Center for Biotechnology, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Arata
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onimaru
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000378:metabolism; D003645:Death, Sudden / Q000209:etiology*; D015870:Gene Expression; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics*; D012119:Respiration / Q000235:genetics; D012125:Respiratory Center / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: C495402:Adcyap1 protein, mouse; D002395:Catecholamines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014446:Tyrosine 3-Monooxygenase