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

International Journal of Developmental Neuroscience - Tập 12 - Trang 117-125 - 1994
L.C. Plantinga1, J. Verhaagen1, S.L. Wong1, P.M. Edwards2, P.R. Bär3, W.H. Gispen1
1Rudolf Magnus Institute, Department of Pharmacology, Utrecht University, Vondellaan 6, 3521 GD Utrecht, The Netherlands
2Molecular Genetics Unit, Bacteriology Department, Ministry of Agriculture, Fisheries and Food, Central Veterinary Laboratory, New Haw, Weybridge, Surrey, U.K.
3Department of Neurology, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

Tóm tắt

AbstractThe 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. Dot blots containing RN A samples of DRG, spinal cord or sciatic nerve of control animals, saline treated and Org 2766 treated animals isolated 15 min, 30 min, l hr, 1 day and 2 days following nerve crush were scanned densitometrically. No significant effect of Org 2766 on the expression of c‐fos mRNA was detected. We conclude that Org 2766 does not stimulate peripheral nerve regeneration by affecting the expression of the c‐fos mRNA following sciatic nerve crush. The putative effect of Org 2766 on other immediate early transcription factors of the fos and jun family is currently under investigation.

Tài liệu tham khảo

Bär P.R., 1990, Neuropeptides: Basics and Perspectives, 175 Bijlsma W.A., 1984, Neurotrophic factors and regeneration in the peripheral nervous system, Psychoneuroendocrinology, 9, 199, 10.1016/0306-4530(84)90001-5 10.1128/MCB.5.1.167 10.1002/bies.950070606 10.1016/0092-8674(88)90024-4 10.1016/0022-510X(86)90109-7 10.1016/0022-510X(84)90181-3 10.1016/0277-5379(88)90293-3 10.1016/0168-3659(90)90010-Q Greenberg S.G., 1988, Neurofilament protein synthesis in DRG neurons decreases more after peripheral axotomy than after central axotomy, J. Neurosci., 8, 1739, 10.1523/JNEUROSCI.08-05-01739.1988 10.1016/0169-328X(92)90170-G Hoffman P.N., 1989, Expression of GAP‐43, a rapidly transported growth‐associated protein, and class 2 beta tubulin. a slowly transported cytoskeletal protein, are coordinated in regenerating neurons, J. Neurosci., 9, 893, 10.1523/JNEUROSCI.09-03-00893.1989 Hol E.M., 1992, Induction of c‐fos protein and mRNA in fetal rat spinal cord cells after treatment with α‐MSH in vitro, J. Neurol., 239, S31 10.1097/00001756-199306000-00012 10.1016/0304-3940(88)90732-X 10.1038/328632a0 10.1016/0304-3940(91)90731-8 10.1016/0006-8993(91)91699-2 10.1146/annurev.ne.14.030191.002225 10.1016/0169-328X(92)90203-N Pyykonen I., 1991, c‐fos protein like immunoreactivity in non‐neuronal cells of rat peripheral nerve after transection, Acta Neuropathol., 82, 66, 10.1007/BF00310925 10.1097/00001756-199206000-00002 10.1083/jcb.89.1.86 10.1016/0014-2999(90)90432-6 10.1016/0301-0082(89)90035-X 10.1016/0196-9781(88)90082-4 10.1016/0196-9781(92)90015-U 10.2337/diabetes.38.2.225 10.1016/0196-9781(87)90028-3 10.1016/0006-8993(87)91365-5 10.1016/0896-6273(90)90118-Y
Thông tin
Thông tin xuất bản

International Journal of Developmental Neuroscience

Tập 12

117-125

Thông tin tác giả