title: Neuroprotective fibroblast growth factor type-2 down-regulates the c-Jun transcription factor in axotomized sympathetic preganglionic neurons of adult rat.
abstract: The immediate-early gene encoded transcription factor c-Jun is highly inducible following axotomy and therefore serves as a valuable marker in neuronal de- and regeneration. As the signals that may trigger c-Jun expression are still obscure, molecules derived from lesioned neurons and/or their targets such as growth factors or cytokines have been proposed as candidates for interneuronal transcriptional regulation in vivo. We therefore tested whether local administration of the neuroprotective cytokine fibroblast growth factor type-2 in vivo has an effect on the axotomy-induced nuclear expression patterns of the activator protein-1 transcription factors c-Fos and JunB, or c-Jun in the spinal cord-intermedolateral nucleus-adrenal axis lesion paradigm in the rat. Partial axotomy of preganglionic nerve fibres by selective unilateral removal of the adrenal medulla resulted in strong staining patterns of c-Jun in the nuclei of preganglionic cell bodies located in the spinal intermediolateral cell column identified by in vivo retrograde prelabelling with the fluorescent tracer Fast Blue prior to lesion. Axotomy-induced nuclear c-Jun expression was highly increased when compared with the moderate baseline expression in normal or sham-operated animals. In animals treated with fibroblast growth factor-2 gelfoams implanted to the lesioned adrenal gland the nuclear c-Jun staining pattern is reduced or even absent from these neurons. By contrast, c-Fos and JunB induction did not occur in the intermediolateral nucleus in the lesion paradigm investigated. These results support the idea of functional links between neurotrophic cytokines such as fibroblast growth factor-2 and transcriptional effectors such as c-Jun. The target derived fibroblast growth factor-2 thus may signal the intactness of the neuron-target axis resulting in suppression of central extrinsic neurons and promotion of neuroprotective gene activation. Neuronal survival in absence of c-Jun indicates that c-Jun exerts negative actions in vulnerated neurons.
authors.affiliation: Department of Anatomy, Benjamin Franklin University Clinics, Freie Universität Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Blottner
authors.forename: T
authors.initials: T
authors.lastname: Herdegen
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019771:Axotomy; D003574:Cytochrome c Group / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D003574:Cytochrome c Group; D018696:Neuroprotective Agents; D016755:Proto-Oncogene Proteins c-jun; D016222:Fibroblast Growth Factor 2