Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency
Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency
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DOI：
10.1007/978-1-4419-5692-7_3
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Arata, Akiko
中科院分区：
文献类型：
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作者：
Amano, Kenji;Fujii, Morimitsu;Arata, Akiko
唐氏细胞粘附分子（Down syndrome cell adhesion molecule， DSCAM）是一种神经粘附分子，在神经发育过程中发挥多种作用。我们破坏了小鼠的Dscam基因座，发现零突变体（Dscam(-/-)）在出生后24小时内死亡。在零突变体中，全身体积脉搏图显示呼吸不规则和低通气对高碳酸血症的反应。此外，Dscam（-/-）小鼠的髓-脊髓制备表明，C4腹侧根活动（驱动膈肌收缩以获得灵感）具有不规则的节律，并伴有频繁的呼吸暂停。在Dscam（-/-）小鼠中，使用电压敏感染料的光学成像显示，位于吻侧腹侧延髓（RVLM）的呼吸前（Pre-I）神经元（属于呼吸节律发生器）失去了同步性。存活到成年没有明显异常的Dscam（+/-）小鼠也表现出呼吸不规则，但比Dscam（-/-）小鼠温和。这些结果表明，DSCAM在中枢呼吸调节中起着剂量依赖性的关键作用。这些结果已经发表（Amano et al. 2009）。
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 hours after birth. Whole body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Further, 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 (Pre-I) neurons located in the rostral ventrolateral medulla (RVLM) 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. These results have been published (Amano et al. 2009).