The induction of c-fos mRNA was assessed using Northern blots and in situ hybridization in adult rats administered hypertonic saline (HS) and isotonic saline (IS). HS induced c-fos mRNA in magnocellular paraventricular nucleus (PVNm), parvocellular paraventricular nucleus (PVNp), supraoptic nucleus (SON), and lamina terminalis (LMT). This occurred within 5 min, peaked at 30-60 min, and disappeared by 180 min. Fos protein, detected using a specific monoclonal antibody, was maximal at 1-2 hr and disappeared 4-8 hr after HS administration. This confirms observations showing that the c-fos gene response is transient even in the presence of a continuing stimulus. In contrast, Fos-like immunoreactivity (FLI), detected using two polyclonal antisera, was observed in PVNm, PVNp, SON, and LMT for 1-24 hr during continuous osmotic stimulation. Moreover, FLI was observable in these structures for 7 d in rats administered HS and allowed to drink water ad libitum beginning 24 hr later. At times greater than 8 hr, FLI presumably represents Fos-related antigens (FRA), proteins immunologically and functionally related to Fos, whose expression is much more prolonged than authentic Fos following the osmotic stimulus. In addition to induction of c-fos expression in regions specifically involved in osmotic regulation, HS injections also induced c-fos in many other forebrain regions. In order to assess the induction of c-fos mRNA due to the "stress" of the injections, rats injected with isotonic saline were compared to uninjected controls. Isotonic saline injections induced c-fos mRNA in the PVNp, anterior hypothalamus, suprachiasmatic nucleus, cingulate gyrus, neocortex, ventral lateral septal nucleus, piriform cortex, hippocampal pyramidal and dentate granule neurons, paraventricular and intralaminar thalamic nuclei, bed nuclei of stria terminalis, cortical and medial amygdaloid nuclei, and other structures. In accord with other work, we interpret this pattern of c-fos expression to result from the stress of handling and injections. Since Fos and FRA probably bind to the promoters of target genes and regulate their expression, they likely mediate biochemical changes in the cells activated by the osmotic and stressful stimuli. Whereas the Fos signal is transient, FRA may act on target genes for the duration of the stimulus or longer.

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The expression of the c-jun, c-fos, and NGFI-A genes was studied in the rabbit retina after optic nerve crush (ONC) or an intravitreal injection of colchicine. By Northern blotting, the basal expression of c-fos and NGFI-A mRNAs were undetectable, whereas c-jun mRNA showed a low basal expression in sham-operated control retinas. Very few or no Jun- or Fos-immunoreactive nuclei were seen in control retinas. From 1 to 95 days after ONC a marked induction of JUN- but not FOS-immunoreactive neurons was seen in the ganglion cell layer peaking at 3 and 7 days. Jun-positive neurons also accumulated immunoreactive phosphorylated neurofilaments, indicating that they were ganglion cells. Northern blots demonstrated that retinal levels of c-jun mRNA, but not of c-fos or NGFI-A mRNAs, were increased 3 and 7 days after ONC. An intravitreal injection of colchicine also induced Jun-immunoreactivity within 24 hr in most of the neurons in the ganglion cell layer, but not in the inner nuclear and outer nuclear layers. The results indicate that axonal damage induces a specific pattern of IEG expression including a long-term induction of the c-jun gene in CNS neurons.