Glutamate receptor agonist kainate enhances primary dendrite number and length from immature mouse cortical neurons in vitro
Glutamate receptor agonist kainate enhances primary dendrite number and length from immature mouse cortical neurons in vitro
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DOI：
10.1002/jnr.20805
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
Le Roux, PD
中科院分区：
文献类型：
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作者：
Monnerie, H;Le Roux, PD
谷氨酸是树突发育的重要调节因子，可能抑制（在缺血性损伤期间）或促进（在早期发育期间）树突生长。以往的研究主要报道谷氨酸介导的n -甲基- d -天冬氨酸（NMDA）受体对树突生长的促进作用。在这项研究中，我们研究了非nmda受体激动剂海盐酸盐如何影响树突生长。体外培养E18小鼠皮质神经元3 d，用抗微管相关蛋白2 （MAP2）和抗神经丝（NF-H）进行免疫标记，分别识别树突和轴突。皮质神经元暴露于海钠酸盐中可增加树突生长，但不影响神经元存活。这种作用具有剂量依赖性和可逆性，可被α -氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AMPA)/盐酸盐受体拮抗剂NBQX和低亲和的盐酸盐受体拮抗剂NS102阻断，但不被AMPA受体拮抗剂CFM-2阻断。此外，NMDA受体拮抗剂MK-801对盐酸盐诱导的树突生长没有影响。使用GluR6和KA2亚基抗体对海碱盐受体进行免疫标记和Western blot分析，表明本研究中使用的未成熟皮质神经元表达海碱盐受体蛋白。这些结果表明，kainate诱导的非nmda受体激活促进了体外未成熟皮质神经元的树突生长，特别是初级树突的数量和长度，kainate受体可能直接参与了这一过程。此外，这些数据支持了一种可能性，即像NMDA受体一样，海碱盐受体的激活也可能有助于体外皮层神经元的早期神经突生长。(c) 2006 Wiley-Liss, Inc。
Glutamate is an important regulator of dendrite development that may inhibit, (during ischemic injury), or facilitate (during early development) dendrite growth. Previous studies have reported mainly on the N-methyl-D-aspartate (NMDA) receptor-mediated dendrite growth-promoting effect of glutamate. In this study, we examined how the non-NMDA receptor agonist kainate influenced dendrite growth. E18 mouse cortical neurons were grown for 3 days in vitro and immunolabeled with anti-microtubule-associated protein 2 (MAP2) and antineurofilament (NF-H), to identify dendrites and axons, respectively. Exposure of cortical neurons to kainate increased dendrite growth without affecting neuron survival. This effect was dose-dependent, reversible and blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/kainate receptor antagonist NBQX and the low-affinity kainate receptor antagonist NS102, but not by the AMPA receptor antagonist CFM-2. In addition, the NMDA receptor antagonist MK-801 had no effect on kainate-induced dendrite growth. Immunolabeling and Western blot analysis of kainate receptors using antibodies against the GluR6 and KA2 subunits, demonstrated that the immature cortical neurons used in this study express kainate receptor proteins. These results suggest that kainate-induced non-NMDA receptor activation promotes dendrite growth, and in particular primary dendrite number and length, from immature cortical neurons in vitro, and that kainate receptors may be directly involved in this process. Furthermore, these data support the possibility that like NMDA receptors, kainate receptor activation may also contribute to early neurite growth from cortical neurons in vitro. (c) 2006 Wiley-Liss, Inc.