Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus
Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus
复制标题
DOI：
10.1523/jneurosci.3290-04.2004
复制
发表时间：
2004-10-20
影响因子：
5.3
通讯作者：
Corriveau, RA
中科院分区：
文献类型：
--
作者：
Adams, SM;Vaccari, JCD;Corriveau, RA
NMDA谷氨酸受体的遗传缺失破坏了躯体感觉系统中与须相关的神经元模式的发育。独立的研究表明，NMDA受体拮抗剂增加发育中的神经元细胞死亡。在这里，我们报告说，一个显着的特点，在新生儿NMDA受体1（NMDAR 1）基因敲除小鼠的体感系统的发展是增加丘脑腹侧基底核（VB）的细胞死亡。对切片进行末端脱氧核苷酸转移酶dUTP缺口末端标记染色以检测凋亡DNA片段化，进行硫代巴比妥染色以检测固缩核，进行银染色以检测变性细胞，并进行半胱天冬酶-3免疫染色。所有四种方法都表明，NMDAR 1的缺失导致VB中细胞死亡的大量增加（大约三倍至五倍）。NMDA受体拮抗剂地佐环平马来酸盐（MK-801）和苯环利定也增加了这种结构中的细胞死亡。在没有NMDA受体功能的情况下，VB中细胞死亡增加的开始大约是出生的时间，与自然发生的细胞死亡和突触发生重叠，并显示出一些解剖学特异性。例如，在NMDAR 1敲除小鼠的海马或新皮质中，在检查的任何时间点：胚胎第15.5天（E15.5）、E17.5和出生后第0天，细胞死亡没有增加。我们还报告了一个显着减少的VB的大小是明显的E17.5开始。结果表明，NMDA受体在VB中自然发生的细胞死亡过程中对细胞存活起主要作用，并表明细胞死亡是NMDA受体敲除研究中的一个考虑因素。
Genetic deletion of NMDA glutamate receptors disrupts development of whisker-related neuronal patterns in the somatosensory system. Independent studies have shown that NMDA receptor antagonists increase cell death among developing neurons. Here, we report that a dramatic feature of the developing somatosensory system in newborn NMDA receptor 1 (NMDAR1) knock-out mice is increased cell death in the ventrobasal nucleus (VB) of the thalamus. Sections were subject to terminal deoxynucleotidyl transferase dUTP nick end labeling staining for apoptotic DNA fragmentation, thionine staining for pyknotic nuclei, silver staining for degenerating cells, and immunostaining for caspase-3. All four methods demonstrated that deletion of NMDAR1 causes a large ( on the order of threefold to fivefold) increase in cell death in the VB. The NMDA receptor antagonists dizocilpine maleate (MK-801) and phencyclidine also increase cell death in this structure. The onset of increased cell death in the VB in the absence of NMDA receptor function is approximately the time of birth, overlaps with naturally occurring cell death and synaptogenesis, and displays some anatomical specificity. For example, there was no increase in cell death in the hippocampus or neocortex of NMDAR1 knock-out mice at any of the time points examined: embryonic day 15.5 (E15.5), E17.5, and postnatal day 0. We also report a significant reduction in the size of the VB that is evident starting at E17.5. The results indicate that NMDA receptors play a major role in cell survival during naturally occurring cell death in the VB and demonstrate that cell death is a consideration in NMDA receptor knock-out studies.