Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The demonstration that the immediate-early gene c-fos is rapidly and transiently expressed in brain following a variety of manipulations has led to intense study of these genes to determine what physiological role they play. The very wide range of stimuli which lead to induction of immediate-early genes (IEGs) in the brain has raised concerns for the specificity of their actions and the suggestion that they might merely be involved in housekeeping functions. On the other hand, there is evidence that these genes may play a role in the transmission of information from cell surface receptors to the genetic material in many instances of neuronal plasticity, including development of seizure susceptibility (kindling), long-term potentiation, drug-induced changes, the phase shift in circadian rhythms, and spreading neuronal depression. In addition to being a putative third (or fourth) messenger involved in transduction of signals to the genetic material, activation of IEGs has proven to be a useful tool for the study of transsynaptic activation of certain neuronal pathways in the brain. Thus, studies on the induction of IEGs are proving to be especially useful in understanding some important functions and properties of the mammalian brain.
 ...
PMID:Immediate-early genes, neuronal plasticity, and memory. 148 50

In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
 ...
PMID:Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain. 154 93

Experiments were designed to examine in vivo changes in total transcription and in the expression of the c-fos gene following whole-body exposure of mice to JANUS fission-spectrum neutrons. Radiation repair-deficient (wst/wst) and -proficient (wst/., C57BL/6 x C3H F1) mice were exposed to JANUS fission-spectrum neutrons calibrated to deliver a gut dose of 50 cGy. Animals were sacrificed less than 10 or at 60 min postirradiation, and gut tissues were removed for study. Our results revealed that, in repair-proficient mice, an immediate depression (relative to untreated control) in total transcription was evident that continued through 1 h postirradiation. Conversely, radiation-sensitive wst/wst mice displayed doubled transcription levels postirradiation. Expression of c-fos was consistently depressed following radiation exposure in control and wst/wst mice. However, the depression of c-fos mRNA was delayed in wst/wst mice relative to controls. These results demonstrate abnormal regulation of transcription and of c-fos mRNA accumulation in repair-deficient wasted mice following exposure to ionizing radiation. In addition, this work documents rapid total transcriptional depression in normal mice following radiation exposure.
 ...
PMID:Differential effect of ionizing radiation on transcription in repair-deficient and repair-proficient mice. 169 64

Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.
 ...
PMID:The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury. 169 51

Previous work by others has demonstrated that neocortical injury results in the induction of c-fos protooncogene both at and distal to the site of injury. However, secondary effects of focal brain injury, such as spreading depression and seizure activity, also have been shown to induce the expression of c-fos. Thus, it is unclear whether the stimulus inducing c-fos expression after generalized brain trauma is direct neuronal injury or associated, secondary effects of injury. In this study, we tested the hypothesis that a specific axonal disconnection would induce the expression of c-fos proto-oncogene in the injured neurons. The injury paradigm that was used was peripheral axotomy of rodent facial motoneurons. The right facial nerve was severed distal to the stylomastoid foramen, with the left side serving as an internal control. As positive controls, in a separate group of animals, seizures were invoked using bicuculline administered intraperitoneally. At the end of postoperative survival times ranging from 30 min to 24 hr, the animals were sacrificed. For northern blot analysis using a c-fos cDNA probe, total RNA was isolated from the dissected facial nuclear groups in the injury experiments, or whole brain and neocortex in the seizure experiments. For immunocytochemical analysis using a battery of c-fos antibodies, the animals were perfused with paraformaldehyde and processed for routine light microscope immunocytochemistry. In the bicuculline-injected animals, c-fos mRNA was massively induced in whole brain in a manner proportional to the overall level of gross seizure activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential neuronal expression of c-fos proto-oncogene following peripheral nerve injury or chemically-induced seizure. 190 55

Focal brain injury in mice induced c-fos mRNA and protein in neurons throughout the damaged neocortex, including the piriform and the entorhinal cortices, as well as in nonneural brain cells (e.g., glia, pia, ependyma). The pattern of c-fos induction after injury suggested that injury led to spreading depression which then led to c-fos induction in neurons. Human neurons in the temporal cortex and hippocampus also showed c-fos protein induction after neurosurgical trauma. The c-fos mRNA and protein induction in mouse neurons was prevented by the noncompetitive NMDA antagonist ketamine but only partially inhibited by the voltage-dependent calcium channel antagonist nifedipine and the calmodulin antagonist trifluoperazine. The c-fos protein induction in nonneural brain cells after injury was not affected by these drugs. Thus, induction of c-fos in neocortical neurons after focal brain injury is partly NMDA receptor mediated.
 ...
PMID:Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization. 210 45

The proto-oncogene c-fos is activated in the brain by a variety of stimuli including brain injury. In unilateral brain injury, c-fos immunoreactivity is confined to the damaged hemisphere, an effect reminiscent of spreading depression. Here we show that topical application of KCl (3 M) to the brain surface (which induces spreading depression) is accompanied by ipsilateral increase in c-fos immunolabeling. The activation of c-fos, like spreading depression, is markedly reduced by the non-competitive NMDA antagonist MK-801 (3 mg/kg i.p.).
 ...
PMID:Application of potassium chloride to the brain surface induces the c-fos proto-oncogene: reversal by MK-801. 215 25

Normal human peritoneal macrophages show a restricted capacity to differentiate into inflammatory macrophages in vivo. We now report that these cells are unable to cap and internalize HLA-DR, as compared to endometriosis, and other macrophages. Immunoelectron microscopy indicated that lack of modulation was not due to the presence of preclustered antigenic sites. Northern blot analysis demonstrated transcripts for HLA.DR, c-fms, and c-fos, indicating that the surface defects were not likely to be associated with a general depression of transcriptional activity. There was no correlation between the mobility of class II molecules and the ability to present antigen as determined by autologous lymphocyte responses to tetanus toxoid. The inability of normal peritoneal macrophages to modulate class II antigens may represent a normal and more general environmental alteration required to permit peritoneal cells a scavenging function without developing the deleterious effects leading to a peritoneal inflammatory response.
 ...
PMID:Normal human peritoneal macrophages are unable to cap and internalize class II antigens. 340 27

Levels of mRNA for c-fos, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), TrkB, and TrkC were studied using in situ hybridization in the rat brain at different reperfusion times after unilateral middle cerebral artery occlusion (MCAO). Short-term (15 min) MCAO, which does not cause neuronal death, induced elevated BDNF mRNA expression confined to ipsilateral frontal and cingulate cortices outside the ischemic area. With a longer duration of MCAO (2 h), which leads to cortical infarction, the increase was more marked and elevated BDNF mRNA levels were also detected bilaterally in dentate granule cells and CA1 and CA3 pyramidal neurons. Maximum expression was found after 2 h of reperfusion. At 24 h BDNF mRNA expression had returned to control values. In the ischemic core of the parietal cortex only scattered neurons were expressing high levels of BDNF mRNA after 15 min and 2 h of MCAO. Analysis of different BDNF transcripts showed that MCAO induced a marked increase of exon III mRNA but only small increases of exon I and II mRNAs in cortex and hippocampus. In contrast to BDNF mRNA, elevated expression of c-fos mRNA was observed in the entire ipsilateral cerebral cortex, including the ischemic core, after both 15 min and 2 h of MCAO. Two hours of MCAO also induced transient, bilateral increases of NGF and TrkB mRNA levels and a decrease of NT-3 mRNA expression, confined to dentate granule cells. The upregulation of BDNF mRNA expression in cortical neurons after MCAO is probably triggered by glutamate through a spreading depression-like mechanism. The lack of response of the BDNF gene in the ischemic core may be due to suppression of signal transduction or transcription factor synthesis caused by the ischemia. The observed pattern of gene expression after MCAO agrees well with a neuroprotective role of BDNF in cortical neurons. However, elevated levels of NGF and BDNF protein could also increase synaptic efficacy in the postischemic phase, which may promote epileptogenesis.
 ...
PMID:Regulation of brain-derived neurotrophic factor gene expression after transient middle cerebral artery occlusion with and without brain damage. 758 36

This experiment examined the effects of acute or chronic administration of the antidepressant drug desipramine on conditioned stress-induced behaviors and regional c-fos expression in the brain. To this end, rats were exposed to three sequential daily sessions of uncontrollable foot-shock and matched, on the basis of crouching, into one of four groups. Two of these groups were exposed to saline injections twice daily and two were exposed to injections of desipramine (5 mg/kg, SC) twice per day, for 9 days. On the 10th day one of the saline groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Likewise, on the 10th day one of the desipramine groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Detailed behavioral analysis showed that compared to the saline-treated controls only the group treated chronically with desipramine, including on the test day, exhibited statistically significant reductions in crouching and increases in exploration during the test session. Similarly, Fos immunohistochemistry revealed that the chronic desipramine group showing positive behavioral effects was the only group in which there were significant reductions in the number of stress-induced Fos-positive neurons in five of 60 structures surveyed. These structures included the anterior cingulate cortex, anterior claustrum, central nucleus of the amygdala, dentate gyrus of the dorsal hippocampus, and paraventricular nucleus of the thalamus. To the extent that repeated exposure to uncontrollable stress is an animal model of depression, these and previous results suggest that these structures are potentially important neural targets for the antidepressant effects of desipramine.
 ...
PMID:Chronic desipramine alters stress-induced behaviors and regional expression of the immediate early gene, c-fos. 766 49


1 2 3 4 5 6 7 8 9 10 Next >>