NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury.
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.
Josephson
A
A
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Widenfalk
J
J
Widmer
H W
HW
Olson
L
L
Spenger
C
C
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D005333:Fetus; D005724:Ganglia / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D009046:Motor Neurons / Q000378:metabolism; D009185:Myelin Proteins / Q000032:analysis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D000070798:Nogo Proteins; D009928:Organ Specificity; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016474:Weight-Bearing
D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat; D007608:Kainic Acid