Analysis of the central respiratory disorder in PACAP-deficient mice

垂体腺苷环化酶激活多肽(PACAP)是一种在神经组织中广泛表达的神经肽。PACAP基因敲除(-/-)小鼠表现出类似婴儿猝死综合征(SID)的表型，尽管解释这一现象的潜在生理机制仍不清楚。在此，我们报道了PACAP-/-小鼠在低氧条件下存在呼吸活动异常的情况，这为SIDS样表型提供了基础。与野生型动物相比，PACAP-/-小鼠的基线呼吸活动降低，对缺氧的反应异常。组织学和实时定量聚合酶链式反应分析表明，PACAP-/-小鼠延髓儿茶酚胺能系统受损，提示内源性PACAP通过作用于儿茶酚胺能系统影响延髓呼吸中枢。我们认为，这一系统的破坏可能与PACAP-/-小鼠的婴儿猝死样表型有关。因此，参与O_2感觉的儿茶酚胺能系统的紊乱可能与SIDS的潜在神经机制有关。

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.