Analysis of the central respiratory disorder in PACAP-deficient mice

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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 reporton 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. Histological and real time PCR analyses indicated that the catecholaminergic system in the medulla was impaired in PACAP-/- mice, suggesting that endogenous PACAP affects respiratory centers in the medulla via its action on the catecholaminergic system. We propose that disruption of this system may beinvolved in the sudden infant death-like phenotype of PACAP -/- mice. Thus, disorders of the catecholaminergic system involved with O_2sensing could be implicated in underlying neuronal mechanisms responsible for SIDS.