DSCAM Deficiency Causes Loss of Pre-Inspiratory Neuron Synchroneity and Perinatal Death
DSCAM Deficiency Causes Loss of Pre-Inspiratory Neuron Synchroneity and Perinatal Death
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DOI：
10.1523/jneurosci.3624-08.2009
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发表时间：
2009-03-04
影响因子：
5.3
通讯作者：
Yamakawa, Kazuhiro
中科院分区：
文献类型：
--
作者：
Amano, Kenji;Fujii, Morimitsu;Yamakawa, Kazuhiro
唐氏综合征细胞粘附分子（DSCAM）是一种神经粘附分子，在神经发育中发挥着多种作用。我们在小鼠中破坏Dscam位点，发现无效突变体（Dscam（-/-））在出生后24小时内死亡。全身体积描记法显示无效突变体对高碳酸血症的不规则呼吸和较低的呼吸反应。此外，Dscam（-/-）小鼠的髓质-脊髓制备显示，驱动膈肌收缩以进行吸气的C4腹根活动具有不规则的节律，伴有频繁的呼吸暂停。使用电压敏感染料的制备的光学成像显示，位于延髓头端腹外侧区的吸气前神经元，属于呼吸节律发生器，在Dscam（-/-）小鼠中失去了它们的同步性。Dscam（-/-）小鼠存活至成年，没有任何明显的异常，也显示出呼吸不规则，但比Dscam（-/-）小鼠轻。这些结果表明，DSCAM在中枢呼吸调节中起着重要作用，并呈剂量依赖性。
Down syndrome cell adhesion molecule (DSCAM) is a neural adhesion molecule that plays diverse roles in neural development. We disrupted the Dscam locus in mice and found that the null mutants (Dscam(-/-)) died within 24 h after birth. Whole-body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Furthermore, a medulla-spinal cord preparation of Dscam(-/-) mice showed that the C4 ventral root activity, which drives diaphragm contraction for inspiration, had an irregular rhythm with frequent apneas. Optical imaging of the preparation using voltage-sensitive dye revealed that the pre-inspiratory neurons located in the rostral ventrolateral medulla and belonging to the rhythm generator for respiration, lost their synchroneity in Dscam(-/-) mice. Dscam(-/-) mice, which survived to adulthood without any overt abnormalities, also showed irregular respiration but milder than Dscam(-/-) mice. These results suggest that DSCAM plays a critical role in central respiratory regulation in a dosage-dependent manner.