INDUCTION OF C-JUN AND SUPPRESSION OF CREB TRANSCRIPTION FACTOR PROTEINS IN AXOTOMIZED NEURONS OF SUBSTANTIA-NIGRA AND COVARIATION WITH TYROSINE-HYDROXYLASE

In adult rats, the expression of transcription factor proteins c-Jun a nd CREB and their colocalization with tyrosine hydroxylase (TH) were i nvestigated in neurons of the substantia nigra compacta (SNC) axotomiz ed by stereotaxic unilateral transection of the medial forebrain bundl e (MFB). Axotomized SNC neurons were identified by injection of the re trograde tracer horseradish-peroxidase-coupled-gold (HRP-gold) into th e ipsilateral striatum 5 days prior to MFB transection. Nuclear c-Jun immunoreactivity (IR) appeared 36 h after MFB transection in SNC neuro ns, was maximal after 5 days, and declined after 10 days. c-Jun-IR was visible in HRP-gold-labeled SNC neurons, demonstrating that c-Jun is in fact expressed in axotomized neurons. The constitutively expressed CREB (calcium/cAMP response element-binding protein, syn. CREB-1) was present in apparently all neuronal and glial cells in the brains of un treated rats including those SNC neurons that coexpressed TH. Three da ys following MFB transection, the nuclear CREB-IR disappeared in the a xotomized SNC neurons labeled by TH-IR and was almost completely absen t after 20 days in this neuronal population. The TH-IR rapidly decline d 5 days after MFB transection, and 10 and 100 days postaxotomy the nu mber of TH-labeled neurons was reduced by 52 and 80%, respectively. Du ring this period, the majority of surviving TH positive neurons coexpr essed c-Jun but were immunonegative for CREB. Between 3 and 60 days fo llowing MFB transection, the number of CREB-labeled glial cell nuclei increased in the ipsilateral substantia nigra by about 80%. Concomitan tly, expression of GFAP, a marker protein for astrocytes, was also enh anced whereas nuclear c-Jun-, JunD-, and c-Fos-IR did not change in gl ial cells. These findings demonstrate that c-Jun can be expressed in a xotomized neurons during the absence of CREB and suggest a role of c-J un in the transcriptional control of the TH gene. (C) 1994 Academic Pr ess, Inc.