Josephson A, Widenfalk J, Widmer H W, Olson L, Spenger C
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Exp Neurol. 2001 Jun;169(2):319-28. doi: 10.1006/exnr.2001.7659.
Nogo is a myelin-associated protein known to inhibit growth of neurites. In order to understand possible physiological roles of Nogo, we performed in situ hybridization using rat and human probes complementary to a Nogo-A-specific sequence and a sequence shared by all known Nogo transcripts recognizing nogo-A, -B, and -C. We studied the cellular distribution of nogo-mRNA in fetal and adult human and rat tissues, with a focus on the spinal cord and ganglia. Rat mRNA expression was also studied in a spinal cord weight-drop model and in animals exposed to kainic acid. In human fetal tissue, nogo-A was strongly expressed in the ventral two-thirds of the spinal cord, the dorsal root ganglia, and autonomic ganglia. Similarly, nogo-A mRNA expression was observed in the adult human spinal cord and ganglia. High levels of nogo-A message were observed in neurons, such as motor neurons and sensory ganglia neurons. The distribution of nogo message in rats resembled that seen in human tissues. Thus, nogo mRNA was expressed in neurons and oligodendrocytes, but not astrocytes or Schwann cells. In addition, expression of nogo-A mRNA was observed in human and rat developing muscle tissue. High level of nogo-mRNA were also expressed in the rat trigeminal ganglion and trigeminal pontine nucleus. In fetal rats the adrenal gland and cell clusters in the liver were positive for the nogo-ABC pan-probe, but negative for the nogo-A probe. While neurons in the adult rat brain were generally positive, very prominent nogo-A mRNA and nogo-ABC mRNA signals were obtained from neurons of the hippocampus, piriform cortex, the red nucleus, and the oculomotor nucleus. Nogo-A mRNA expression was markedly reduced in the epicenter of a lesion in the spinal cord of adult rats 6 and 24 h after a weight-drop injury, while no perifocal upregulation of nogo mRNA was seen. No obvious change of nogo expression was detected in kainic acid exposed animals. In conclusion our in situ hybridization study has demonstrated widespread expression of nogo mRNA in the fetal, developing and adult nervous system of rat and man. In addition to oligodendroglial cells, high levels of nogo-A mRNA expression were found in neurons, raising important questions about the function of neuronal nogo mRNA. No obvious regulation of nogo was detected following injury.
Nogo是一种已知可抑制神经突生长的髓鞘相关蛋白。为了了解Nogo可能的生理作用，我们使用与Nogo-A特异性序列以及所有已知识别Nogo-A、-B和-C的Nogo转录本共有的序列互补的大鼠和人类探针进行了原位杂交。我们研究了Nogo-mRNA在胎儿和成人的人类及大鼠组织中的细胞分布，重点关注脊髓和神经节。还在脊髓重物坠落模型和暴露于 kainic 酸的动物中研究了大鼠mRNA的表达。在人类胎儿组织中，Nogo-A在脊髓腹侧三分之二、背根神经节和自主神经节中强烈表达。同样，在成人人类脊髓和神经节中也观察到了Nogo-A mRNA的表达。在神经元中观察到高水平的Nogo-A信息，如运动神经元和感觉神经节神经元。大鼠中Nogo信息的分布与在人类组织中看到的相似。因此，Nogo mRNA在神经元和少突胶质细胞中表达，但在星形胶质细胞或雪旺细胞中不表达。此外，在人类和大鼠发育中的肌肉组织中观察到了Nogo-A mRNA的表达。大鼠三叉神经节和三叉脑桥核中也表达了高水平的Nogo-mRNA。在胎儿大鼠中，肾上腺和肝脏中的细胞簇对Nogo-ABC泛探针呈阳性，但对Nogo-A探针呈阴性。虽然成年大鼠脑中的神经元通常呈阳性，但从海马体、梨状皮质、红核和动眼神经核的神经元中获得了非常明显的Nogo-A mRNA和Nogo-ABC mRNA信号。在成年大鼠脊髓重物坠落损伤后6小时和24小时，损伤中心的Nogo-A mRNA表达明显降低，而在损伤灶周围未观察到Nogo mRNA的上调。在暴露于 kainic 酸的动物中未检测到Nogo表达的明显变化。总之，我们的原位杂交研究表明，Nogo mRNA在大鼠和人类的胎儿、发育中和成年神经系统中广泛表达。除了少突胶质细胞外，在神经元中还发现了高水平的Nogo-A mRNA表达，这引发了关于神经元Nogo mRNA功能的重要问题。损伤后未检测到Nogo的明显调节。
