The neurotrophic peptide Org 2766 does not influence the expression of the immediate early gene c-fos following sciatic nerve crush in the rat.
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)
Plantinga
L C
LC
Rudolf Magnus Institute, Department of Pharmacology, Utrecht University, The Netherlands.
Verhaagen
J
J
Wong
S L
SL
Edwards
P M
PM
Bär
P R
PR
Gispen
W H
WH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D008969:Molecular Sequence Data; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D012583:Schwann Cells / Q000502:physiology; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology
D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone