Expression of the N-methyl-D-aspartate receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons.
Expression of the N-methyl-D-aspartate receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons.
复制标题
N-甲基-D-天冬氨酸受体亚基 NR3B 的表达调节脊髓运动神经元的树突形态发生。
DOI：
10.1016/j.neuroscience.2008.03.089
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发表时间：
2008
期刊：
影响因子：
3.3
通讯作者：
Inglis,FM
中科院分区：
文献类型：
--
作者：
Prithviraj,R;Inglis,FM
在出生后的发育过程中，脊髓运动神经元的树突以一种活动依赖的方式被完善，这种方式可以通过阻断n -甲基-d-天冬氨酸（NMDA）受体的激活来影响。在出生后晚期，树突细化停止，树突结构不受NMDA拮抗剂的影响；然而，限制枝晶塑性的分子底物尚不清楚。在出生后发育后期，NR3B NMDA受体亚基的表达在运动神经元中上调，该亚基被认为是减少谷氨酸诱导的离子电流的显性负亚基。为了研究NR3B表达增加是否可能导致脊髓活动依赖性树突重组发育后期的缺失，我们在培养的大鼠脊髓运动神经元中过表达NR3B，并比较其对树突形态的影响与药物阻断NMDA受体的影响。我们发现NR3B受体亚基的过表达增加了树突乔木的长度和复杂性，增加了树突丝状足的数量，这表明NR3B促进了运动神经元发育过程中分支段的增加。相比之下，NMDA拮抗剂dl-2-氨基-5-磷酸戊酸酯（AP5）阻断NMDA受体活性对树突乔木的总长度和复杂性影响不大。相反，用AP5处理导致树突乔木的显著重组，以有利于增加高分支阶的树突片段的方式，牺牲了靠近细胞体的树突片段。这些结果表明NR3B亚基的表达可能参与树突结构的活性依赖性重组，但其机制可能与NMDA受体活性的丧失不一致。
During postnatal development, the dendrites of spinal motor neurons are refined in an activity-dependent manner that can be influenced by blocking activation of N-methyl-d-aspartate (NMDA) receptors. In late postnatal life, dendritic refinement ceases, and dendrite architecture is unaffected by NMDA antagonists; however the molecular substrate for limiting dendritic plasticity is not understood. During late postnatal development, expression of the NR3B NMDA receptor subunit, a putative dominant-negative subunit that reduces glutamate-induced ionic currents, is upregulated within motor neurons. To investigate whether increasing NR3B expression may contribute to the loss in late development of activity-dependent dendritic reorganization in the spinal cord, we over-expressed NR3B in cultured rat spinal motor neurons, and compared its effects on dendrite morphology with the effects of pharmacological blockade of NMDA receptors. We found that over-expression of the NR3B receptor subunit increased the length and complexity of dendritic arbor, and increased numbers of dendritic filopodia, suggesting that NR3B promotes the addition of branch segments in developing motor neurons. In contrast, blockade of NMDA receptor activity by the NMDA antagonist dl-2-amino-5-phosphonovalerate (AP5) had little effect on the overall length or complexity of dendritic arbor. Instead, treatment with AP5 resulted in significant reorganization of dendritic arbor in a manner that favored addition of dendritic segments of high branch orders, at the expense of those closer to the cell body. These results suggest that expression of the NR3B subunit may participate in activity-dependent reorganization of dendritic architecture, but via a mechanism that may be inconsistent with loss of NMDA receptor activity.