c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat.
The proto-oncogene c-jun is thought to play a role in the control of growth and differentiation of many cell types. It has been demonstrated previously that damage to axons of peripheral motor or sensory neurons resulted within 24 h in substantially increased levels of the c-jun gene in the parent cell bodies. These increased levels of c-jun protein and messenger RNA are maintained if the damaged nerve is ligated, but return to basal levels if the peripheral nerve is allowed to regenerate. We have examined the expression of immediate early genes in central neurons of the rat and now show that a 6-hydroxydopamine-induced axotomy of the dopaminergic nigrostriatal pathway results in a substantial increase in the levels of c-jun (but not c-fos) messenger RNA and protein within neurons of the substantia nigra pars compacta. However, the central neuronal response differs from the peripheral nerve response in that it becomes maximal at four to eight days post-lesion and is transient, declining to control levels in nigral neurons by 14 days post-lesion. These expression patterns may be related to the differential capacity of central and peripheral neurons to regenerate. The precise role of c-jun in these processes, or in the regenerative response, is unclear but it remains possible that c-jun activation following axon damage leads to an increased expression of genes which are essential for the regenerative response. The nature of the mechanism by which c-jun levels are attenuated in central neurons is also unclear, but inhibitory factors, generated by the central environment, may play a role.
Jenkins
R
R
MRC Molecular Neurobiology Unit, MRC Centre, Cambridge, U.K.
O'Shea
R
R
Thomas
K L
KL
Hunt
S P
SP
D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016758:Genes, jun; D007051:Ibotenic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008454:Mazindol / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D007051:Ibotenic Acid; D016627:Oxidopamine; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase