Basal forebrain neuronal loss in mice lacking neurotrophin receptor p75.
Basal forebrain neuronal loss in mice lacking neurotrophin receptor p75.
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缺乏神经营养素受体 p75 的小鼠的基底前脑神经元损失。
DOI：
10.1126/science.277.5327.837
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Gage,FH
中科院分区：
文献类型：
--
作者：
Peterson,DA;Leppert,JT;Lee,KF;Gage,FH
体外研究有大量证据表明，神经生长因子（NGF）对中枢神经元的发育和存活产生重要影响（1）。NGF的作用被认为是通过高亲和力酪氨酸受体激酶trkA和低亲和力p75受体介导的（2）。几项研究表明，p75受体启动凋亡信号，导致神经元死亡（3）。NGF在完整系统中中枢神经元发育和存活中的作用尚不清楚。无效突变小鼠的使用提供了一个有用的策略，在体内发育过程中的特定受体和因子的作用划定。已经产生了缺乏NGF和trkA的小鼠，并研究了突变对中枢神经元的影响（4）。尽管观察到外周神经元发育受损，但缺乏NGF或缺乏trkA受体都不能阻止隔胆碱能神经元的发育和存活，隔胆碱能神经元是正常表达trkA和p75受体的细胞，并且可以在创伤性病变后通过施用NGF来拯救。然而，这两项研究并没有提供定量数据（4）。我们之前培养了携带p75靶向突变的小鼠，发现这些动物的外周神经系统明显受损（5）。在这里，我们描述了缺乏p75受体对基底前脑中枢神经元的影响。我们使用无偏的定量体视学来避免实验条件和对照条件之间参考体积失真产生的定量伪影（6）。虽然每个组织学切片的细胞数量是感兴趣的表观值，但切片只是被检查的整个结构的样本。表达相对于组织切片的定量值可能导致两个定量伪影。第一种，称为过度投影和截断，是由于在样品（聚焦）平面内错误地识别细胞造成的。多年来，这是纠正使用数学模型，如阿伯克龙比方法，但现在更好地解决了使用的解剖原则
There is substantial evidence from in vitro studies that nerve growth factor (NGF) exerts an important influence on the development and survival of central neurons (1). The effects of NGF are thought to be mediated through the high-affinity tyrosine receptor kinase trkA and the low-affinity p75 receptor (2). Several studies suggest that the p75 receptor initiates an apoptotic signal that leads to neuronal death (3). The role of NGF in the development and survival of central neurons in intact systems is less clear. The use of null mutant mice provides a useful strategy for delineating the role of specific receptors and factors during in vivo development. Mice that are deficient in NGF and trkA have been produced, and the effect of the mutation on central neurons was investigated (4). Despite the observation of impairment of peripheral neuronal development, neither the lack of NGF nor the absence of trkA receptors prevented the development and survival of septal cholinergic neurons, cells that normally express trkA and p75 receptors and that can be rescued by the administration of NGF after traumatic lesion. These two studies, however, did not provide quantitative data (4).We previously generated mice that carry a targeted mutation for p75 and found significant impairment of the peripheral nervous system in those animals (5). Here, we describe the effect of lack of p75 receptor on central neurons in the basal forebrain. We used unbiased quantitative stereology to avoid quantitative artifacts arising from reference volume distortion between experimental and control conditions (6). While the number of cells per histological section is the apparent value of interest, the section is only a sample of the entire structure being examined. Expressing the quantitative values relative to the histological section can result in two quantitative artifacts. The first, known as overprojection and truncation, results from incorrectly identifying cells within the sample (focus) plane. For many years, this was corrected by the use of mathematical models, such as the Abercrombie method, but is now better addressed by the use of the disector principle
影响因子：
56.9
作者：
C. Van der Zee;G. Ross;R. Riopelle;T. Hagg
通讯作者：
C. Van der Zee;G. Ross;R. Riopelle;T. Hagg
p75 缺陷的胚胎背根感觉神经元和新生儿交感神经元对 NGF 的敏感性降低。
DOI：
10.1242/dev.120.4.1027
发表时间：
1994
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Lee,KF;Davies,AM;Jaenisch,R
通讯作者：
Jaenisch,R
影响因子：
56.9
作者：
RABIZADEH, S;OH, J;BREDESEN, DE
通讯作者：
BREDESEN, DE