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-spe cific sequence and a sequence shared by all known Nogo transcripts recogniz ing nogo-A, -B, and -C, We studied the cellular distribution of nogo-mRNA i n fetal and adult human and rat tissues, with a focus on the spinal cord an d ganglia. Rat mRNA expression was also studied in a spinal cord weight-dro p 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 expressi on 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 se en in human tissues, Thus, nogo mRNA was expressed in neurons and oligodend rocytes, but not astrocytes or Schwann cells. In addition, expression of no go-A mRNA was observed in human and rat developing muscle tissue. High leve l of nogo-mRNA were also expressed in the rat trigeminal ganglion and trige minal 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 n ogo-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 neu rons of the hippocampus, piriform cortex, the red nucleus, and the oculomot or 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 i njury, while no perifocal upregulation of nogo mRNA was seen. No obvious ch ange of nogo expression was detected in kainic acid exposed animals. In con clusion our in situ hybridization study has demonstrated widespread express ion of nogo mRNA in the fetal, developing and adult nervous system of rat a nd man. In addition to oligodendroglial cells, high levels of nogo-A mRNA e xpression were found in neurons, raising important questions about the func tion of neuronal nogo mRNA. No obvious regulation of nogo was detected foll owing injury. (C) 2001 Academic Press.