Time Course Of C-fos Expression Research Articles

Spatiotemporal characteristics of pain-associated neuronal activities in primary somatosensory cortex induced by peripheral persistent nociception

The primary somatosensory cortex (S1 area) is one of the key brain structures for central processing of somatic noxious information to produce pain perception. However, so far, the spatiotemporal characteristics of neuronal activities associated with peripheral persistent nociception have rarely been studied. In the present report, we used c-Fos as a neuronal marker to analyze spatial and temporal patterns of pain-related neuronal activities within the S1 area of rats subjecting to subcutaneous (s.c.) injection of bee venom (BV) solution, a well-established animal model of persistent pain. In naïve and saline-treated rats, c-Fos-labeled neurons were diffusely and sparsely distributed in the hindlimb region of S1 area. Following s.c. BV injection, c-Fos-labeled neurons became densely increased in superficial layers (II–III) and less increased in deep layers (IV–VI). The mean number of c-Fos positive neurons in the layers II–III began to increase at 1h and reached a peak at 2h after BV treatment that was followed by a gradual decrease afterward. The time course of c-Fos expression in the layers IV–VI was in parallel with that of the superficial layers, but with a much lower density and magnitude. The present results demonstrated that BV-induced peripheral persistent nociception could evoke increased neuronal activities in the S1 area with predominant localization in layers II–III.

Differential Activation of c‐fos Immunoreactivity After Hypophysectomy in Developing and Adult Rats

The aim of the present study is to compare c-fos expression in identified hypothalamic vasopressin (AVP) and oxytocin (OT) neurons in developing (PN7 and PN14) and adult rats following hypophysectomy using dual-labeled immunostaining. Our results showed that hypophysectomy induced c-fos expression in supraoptic (SON) and paraventricular (PVN) nuclei in both the developing and adult rats. Few or no positive cells were observed in the same nuclei in sham-operated animals. Quantitative analysis for c-fos and either of the above named neuropeptides revealed that almost all AVP and OT neurons in the adult and PN14 groups expressed c-fos in response to hypophysectomy. In PN7, hypophysectomy also induced all AVP neurons to express c-fos in SON and PVN. However, few OT neurons in the SON and PVN produced c-fos after hypophysectomy. In addition, the time course of c-fos expression was different in the developing and adult rats after hypophysectomy. The c-fos expression in the developing rats exhibited a more prolonged induction in which staining for c-fos persisted for at least 3 days after hypophysectomy compared with that in the adult in which c-fos immunoreactivity disappeared within 24 hr post-lesion. This study demonstrates that c-fos expression after hypophysectomy is regulated differently during development.

Time course of c-FOS expression in status epilepticus induced by amygdaloid stimulation.

Decaying of c-FOS immunoreactivity (FIR) was studied in adult rats with 1 h self-sustaining limbic status epilepticus (SSLSE) induced by amygdaloid electrical stimulation. Rats that failed to enter SSLSE showed localized FIR in the ipsilateral limbic cortex, neocortex, and amygdala. FIR became bilaterally extensive, including the hippocampal formation 0.5 h after SSLSE. It decreased gradually between 2 and 6 h and returned to basal levels around 1 day. Neocortical FIR in clonic SSLSE persisted longer than in other types of SSLSE. We demonstrate for the first time that FIR in SSLSE lasts much longer than several hours, its decaying is related to the seizure behavior, and absent or weak FIR at the hippocampal formation is associated with failed SSLSE entry.

C-fos Mediates Cocaine Inhibition of NGF-Induced PC12 Cell Differentiation

In uterococaine exposure can affect CNS development. Previous studies showed that cocaine inhibits neuronal differentiation in a dose-dependent fashion, in nerve growth factor (NGF)-stimulated PC12 cells, without affecting cell viability. NGF activates intracellular signaling proteins, specific immediate-early genes (IEG) including a transient peak of c-fos expression, and induction of late genes expression, leading to the neuronal phenotype. We hypothesized that cocaine interferes with NGF signaling. Therefore, we examined the pattern of c-fos expression in our cellular model. Time course of c-fos expression up to 72 h was determined in cells treated with NGF 20 ng/ml and cocaine 10 μg/ml (a moderately toxic level) by RT-PCR analysis. Total RNA was isolated from cells, and levels of c-fos mRNA were estimated using gene-specific primers. In both control and experimental conditions, c-fos level was maximal at 0.5 h. In the control cells, c-fos expression declined rapidly to less than 5% of the 0.5-h value, while in the cocaine-treated cells, c-fos level persisted through the 72-h exposure. Adding c-fos antisense to cells treated with NGF and cocaine resulted in significant improvement of neurite outgrowth, from 28% (NGF + cocaine) to 89% (NGF + cocaine + c-fos antisense) of control differentiation after 72 h of exposure (Dunnet'sT< 3.24). Inhibitory effects of cocaine on NGF-induced PC12 differentiation may be attributed to alteration of c-fos expression. Further studies will be required to examine the role of D1receptor activation in mediating c-fos expression and to explore the effects of cocaine on other IEGs.

The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter.

The c-fos proto-oncogene is rapidly and transiently induced by a variety of extracellular stimuli. We have previously shown that conditioned media from v-sis transformed NRK cells rapidly induces a DNA binding protein which binds to a conserved sequence upstream of the human c-fos gene. We now show that purified recombinant c-sis/PDGF can induce this binding activity which we have termed SIF, for sis-inducible factor. Oligonucleotides which bind to the SIF protein will confer sis/PDGF inducibility onto a truncated, unresponsive c-fos promoter. However, sequences lying between -100 and -57 of the c-fos gene are required for this induction. The sis-responsive element functions independently of a region of dyad symmetry previously identified as the serum responsive element (SRE). The time course of c-fos expression driven by the sis-responsive element is similar to that mediated by the SRE. Unlike the SRE, which can respond to signals generated by sis/PDGF, serum or phorbol esters, the SIF binding element mediates c-fos induction only in response to sis/PDGF. The SRE and SIF elements function in an additive manner to stimulate the transcription of the c-fos gene in response to sis/PDGF.