The neurotrophic peptide Org 2766 does not influence the expression of the immediate early gene c‐fos following sciatic nerve crush in the rat

Abstract

The neurotrophic peptide Org 2766 accelerates the regeneration of peripheral nerves. Although the mechanism of action of this neuropeptide is not yet understood, functional, pharmacological, and morphological evidence has demonstrated that Org 2766 exerts its beneficial effect during the early stages of nerve regeneration. The induction of some members of the Immediate Early Gene (IEG) family such as c-jun and c-fos is one of the first molecular events following peripheral nerve damage. The Fos and Jun proteins act as a transcription factor and may stimulate the expression of a number of genes implicated in nerve regeneration. We examined whether Org 2766 stimulates nerve regeneration by enhancing or prolonging the expression of c-fos mRNA. Following a crush lesion of the sciatic nerve, the expression of c-fos mRNA was induced in the spinal cord and in the damaged nerve at 30 min following injury in untreated animals as demonstrated with Northern blot. No effect of the crush lesion was observed in dorsal root ganglia (DRG). The induction of c-fos mRNA in the damaged nerve was more robust as compared to the relatively small induction observed in the spinal cord. With in situ hybridization an increase in c-fos mRNA expression both in the dorsal and in the ventral horn of the spinal cord was demonstrated at 30 min post-lesion. In the distal sciatic nerve portion the expression of c-fos mRNA was predominantly localized around Schwann cell nuclei at 30 min after nerve crush. The effect of Org 2766 treatment on the expression of c-fos mRNA was investigated using semiquantitative dot blots.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired activation of celiac ganglion neurons in vivo after damage to their sympathetic nerve terminals

“…Last, we regularly observed nonneuronal staining clearly “ringing” principal neurons, suggesting that at least some of the activated cells after 6‐OHDA are satellite cells. The finding that 6‐OHDA chronically elevates Fos in what we believe are satellite cells is consistent with the known effects of distal axon injury to chronically elevate Fos protein production in Schwann cells adjacent to the insult (Plantinga et al, 1994); we extend this concept to include satellite cells, the specialized Schwann cells surrounding principal ganglionic neurons. The chronically elevated Fos in these presumed satellite cells following 6‐OHDA is also consistent with the finding that satellite cell protrusions grow into the synaptic cleft following axotomy, finalizing the physical separation of sympathetic ganglionic neurons from their presynaptic innervation (Matthews and Nelson, 1975).…”

Peripheral Axotomy Induces Long-Term c-Jun Amino-Terminal Kinase-1 Activation and Activator Protein-1 Binding Activity by c-Jun and junD in Adult Rat Dorsal Root GangliaIn Vivo

“…To determine whether axotomy in vivo induces DNA binding by c-Jun, and to identif y possible partners for c-Jun in DNA binding, we investigated the effect of axotomy on the formation and composition of AP-1 binding complexes in DRGs at various times after injury, using an AP-1 consensus sequence based on the human metallothionein II A (Hmt II A ) promotor in electrophoretic mobility shift assays with antibodies to various jun family members. We did not examine DRGs for AP-1 binding by c-fos, a highly stable partner for c-Jun (Angel and Karin, 1991), because studies using various techniques have not detected this transcription factor in DRGs (Herdegen et al, 1992;Plantinga et al, 1994). ATF2, a member of the CRE-binding protein family, can dimerize with c-Jun to initiate c-Jun transcription from a specialized TRE in the c-Jun promotor (van Dam et al, 1993) but has been shown not to bind to the consensus AP-1 sequence used in our study (Hai and Curran, 1991).…”