Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

c-Fos is a major component of the transcription factor AP-1 which has been implicated in the control of cell proliferation and differentiation as well as in transformation. In order to identify Fos target genes involved in these processes, we have taken advantage of the regulatory properties of the hormone-binding domain of the human estrogen receptor to develop transcriptional and post-translational induction systems, both of which allow selective elevation of Fos activity within a cell. Using this approach we have searched for Fos-responsive genes in rat fibroblasts and PC12 cells. Here we describe the identification and regulation of five Fos-responsive genes encoding a transcription factor (Fra-1), a secreted protein (Fit-1), a biosynthetic enzyme (ODC) and two membrane-associated proteins (annexin II and V), respectively. The post-translational induction system was also used to study the Fos-mediated block of neuronal differentiation of PC12 cells. These experiments demonstrate that Fos activity is dominant over NGF function and interferes with the expression of late NGF-inducible genes.
 ...
PMID:Identification of Fos target genes by the use of selective induction systems. 129 55

Kindling, induced by repeated subconvulsive electrical or chemical stimulations leads to progressive and permanent amplification of seizure activity, culminating in generalized seizures. We report that kindling induced by electrical stimulation in the ventral hippocampus leads to a marked and transient increase in mRNA for NGF and BDNF in the dentate gyrus, the parietal cortex, and the piriform cortex. BDNF mRNA increased also in the pyramidal layer of hippocampus and in the amygdaloid complex. No change was seen in the level of HDNF/NT-3 mRNA. The increased expression of NGF and BDNF mRNAs was not influenced by pretreatment with the NMDA receptor antagonist MK801, but was partially blocked by the quisqualate, AMPA receptor antagonist NBQX. The presumed subsequent increase of the trophic factors themselves may be important for kindling-associated plasticity in specific neuronal systems in the hippocampus, which could promote hyperexcitability and contribute to the development of epileptic syndromes.
 ...
PMID:Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. 182 4

The molecular basis of the axonal reorganization that follows seizure-induced brain injury is unknown. Elevations in neurotrophins following seizures suggest that growth factors may play a role in this process. After pilocarpine-induced seizures, robust axonal sprouting from dentate granule cells and cholinergic forebrain neurons was evident in the inner molecular layer of the dentate gyrus. Intraventricular infusions of an NGF-specific antibody that blocks NGF biological activity in vitro attenuated the cholinergic axonal sprouting and the increases in cell body size of basal forebrain cholinergic neurons that followed seizure-induced injury in vivo. In contrast to its effects on the cholinergic network, the NGF antibody did not decrease the sprouting of dentate granule cell axons into the inner molecular layer. These results suggest that NGF may have a functional and system-specific role in the remodeling of networks that follows repetitive seizures.
 ...
PMID:Selective inhibition of axon outgrowth by antibodies to NGF in a model of temporal lobe epilepsy. 747 61

The NGF-family of neurotrophic factors including NGF, BDNF and NT-3,4/5 is known to be crucial for neuronal survival and differentiation during development. However, recent studies suggest that the neurotrophins are also widely expressed and play a dynamic role in the mature nervous system. One of the major sites of expression of the neurotrophins in the adult brain is the hippocampus which has been also popular as an important structure for the adult plasticity. Moreover, the level of expression of the neurotrophins in the hippocampus can be regulated by a variety of neuronal inputs, such as experimentally-induced seizures, injection of glutamate receptor agonists, and LTP-inducing stimulation. The possibility that the neurotrophins modulate synaptic transmission in the mature brain has been investigated at the Schaffer collateral-CA1 synapses in the adult rat hippocampus. We report that transient application of BDNF and NT-3, but not NGF induces a long-lasting increase of synaptic transmission, which is likely to be mediated by Trk family of receptor tyrosine kinases. Both BDNF and NT-3 decrease paired pulse facilitation, suggesting a possible presynaptic modification. Interestingly, previous potentiation of synaptic activity by the application of neurotrophic factors does not occlude the induction of long-term potentiation. These results suggest that the neurotrophins may locally regulate synaptic plasticity in the adult nervous system.
 ...
PMID:Neurotrophin-induced modulation of synaptic transmission in the adult hippocampus. 758 Dec 94

NGFI-C is an early response gene which encodes a Cys2/His2 zinc finger protein. NGFI-C has previously been demonstrated to be inducible in PC12 cells after NGF stimulation. This study sought to localize this gene in somatosensory cortex, and investigate its possible induction by physiological and seizure stimuli. To determine if NGFI-C message levels are affected by stimulation, RT-PCR was performed on mRNA extracts from somatosensory cortex. NGFI-C mRNA levels were increased to levels four-fold over baseline after a seizure. In a paradigm used as a model of experience-dependent plasticity, vibrissae stimulation also increased the level of NGFI-C expression in the contralateral barrel cortex to 180% of control levels. In situ analysis using digoxigenin-labelled cRNA probes demonstrated NGFI-C containing neurons throughout layers 2 through 6 in somatosensory cortex. A higher cell density was seen after stimulation. Qualitatively, staining was more intense in post-seizure and post-stimulus cortex than in control cortex. Analysis of related zinc finger expression in serial sections revealed that NGFI-C is expressed in a distinct but overlapping cell populations relative to NGFI-A, Krox 20, and Egr-3. These studies demonstrate the inducible nature of NGFI-C message in response to a physiological vibrissae stimulus, as well as to seizures. However, the levels and pattern of expression differ between these two stimuli.
 ...
PMID:NGFI-C expression is affected by physiological stimulation and seizures in the somatosensory cortex. 776 89

The influence of antidepressant treatments on the expression of c-Fos and NGF-1A, two immediate early gene (IEG) transcription factors, was examined. Administration of electroconvulsive seizures (ECS), tranylcypromine, or imipramine, three different classes of antidepressants, increased the expression of c-Fos mRNA and immunoreactivity in rat frontal cortex, but the magnitude of the increase for each treatment differed and the effect of imipramine was preceded by inhibition of c-Fos expression. Expression of NGF-1A was increased by acute or chronic administration of ECS or tranylcypromine, and by chronic (21 d), but not acute, administration of imipramine. To study the mechanisms underlying these differences, we examined the neurotransmitter receptors that regulate the expression of c-Fos. ECS- and tranylcypromine induction of c-Fos immunoreactivity in frontal cortex was partially inhibited by pretreatment with specific antagonists for alpha 1-adrenergic, beta-adrenergic, and 5-HT2A/2C, but not D2-dopamine receptors. ECS induction of c-Fos was also inhibited by D1-dopamine and NMDA glutamate receptor antagonists, suggesting that the greater induction of c-Fos by ECS results from activation of these, and possibly other, neurotransmitter receptors. In the hippocampus, antagonism of tranylcypromine was similar to that in frontal cortex, except the D1-dopamine receptor antagonist also blocked the c-Fos response. In contrast, antagonism of the ECS response in hippocampus was only blocked by the NMDA receptor antagonist. The results demonstrate that ECS- and tranylcypromine induction of c-Fos is mediated by activation of several different neurotransmitter receptors, but that the exact pharmacological profile is different for each treatment and brain region.
 ...
PMID:Regulation of c-Fos and NGF1-A by antidepressant treatments. 909 89

Synaptic activity induces a rapid transcriptional response that is essential for the establishment of long-term neuronal plasticity. Using a differential cloning technique, we have identified a gene induced by seizure activity in the brain as RB3. RB3 is a recently cloned gene belonging to the stathmin family of phosphoproteins. Like SCG10, RB3 is brain-specific, although in situ hybridization results show that the expression of RB3 is more ubiquitous than is that of SCG10. Using genomic DNA sequencing, we show that the 27 amino acid sequence unique to the RB3" transcript is encoded by an alternatively spliced exon, exon 2'. Using a peptide antibody raised against exon 2' to detect RB3" and an anti-Flag antibody to detect an epitope-tagged version of RB3, we show that both proteins are localized to the Golgi apparatus of transfected COS7 cells. Of particular interest, RB3 mRNA, but not SCG10 mRNA, is rapidly induced in the dentate gyrus granule layer of the hippocampus after electrically induced seizure activity as well as stimuli leading to long-term potentiation (LTP). In addition, RB3 mRNA is induced in pheochromocytoma (PC12) cells treated with 250 ng/ml NGF. These results suggest that RB3 may play a role in activity-induced neuronal plasticity and neuronal differentiation.
 ...
PMID:Neuronal activity induction of the stathmin-like gene RB3 in the rat hippocampus: possible role in neuronal plasticity. 982 37

Model studies on animal seizures have proposed potential involvement of the neurotrophins, BDNF and NGF, in human epilepsy. However, their biological significance in this disease itself remains to be evaluated. Here we demonstrate that patients with intractable temporal lobe epilepsy show a marked increase in protein levels of BDNF (2.6-fold, p<0.01) but not other neurotrophins. Moreover, the specific BDNF increase was significantly correlated with contents of neuropeptide Y. Thus, these results indicate the activity-dependent expression of BDNF in human subjects and its potential contribution to the pathophysiology of human epilepsy via neuropeptide Y.
 ...
PMID:Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y. 1008 52

In this study we show that single, physiologically-active and non-convulsive doses of the three GABA(B) receptor antagonists CGP 36742, CGP 56433A and CGP 56999A increase NGF and BDNF mRNA levels by 200-400% and protein levels by 200-250% in rat neocortex, hippocampus as well as spinal cord. In all areas examined the increase in NGF protein preceded that of BDNF. Peak levels of both neurotrophins are transient and occur between 24 and 72 h, depending on the region. In contrast, NT-3 protein concentrations in the neocortex and hippocampus were decreased significantly to 50% of control values within 48-96 h. The decrease in the spinal cord was less than 30% and did not reach significant levels. These data clearly demonstrate that GABA(B) receptor antagonists induce a specific neurotrophin expression in the central nervous system at physiologically relevant doses, as opposed to the extreme conditions of seizure paradigms. The results are in line with the concept that neuronal neurotrophin synthesis and release in brain are controlled by afferent nerve activity. GABA(B) receptor antagonists could therefore be a valuable new approach to selectively increase endogenous neurotrophin levels in the central nervous system.
 ...
PMID:GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats. 1069 11

Neurotrophic growth factors are proteins that control neuronal differentiation and survival, and consequently play important roles in the developing and adult stages of the nervous system. Study of the genes that are regulated by these growth factors has provided insight into the proteins that are critical to the maturation of the nervous system, suggesting that select neurotrophins may play a role in the control of body homeostasis by the brain and peripheral nervous system. Our understanding of the mechanisms of action of neurotrophic growth factors has increased through experimental manipulation of cultured neurons and neuronal cell lines. In particular, the PC12 pheochromocytoma cell line, which displays many properties of adrenal chromaffin cells and undergoes differentiation into sympathetic neuron-like cells when treated with nerve growth factor, has been extensively investigated to identify components of neurotrophin signaling pathways as well as the genes that they regulate. VGF was one of the first neurotrophin-regulated clones identified in NGF-treated PC12 cells. Subsequent studies indicate that the vgf gene is regulated in vivo in the nervous system by neurotrophins, by electrical activity, in response to injury or seizure, and by feeding and the circadian clock. The vgf gene encodes a polypeptide rich in paired basic amino acids; this polypeptide is differentially processed in neuronal and neuroendocrine cells and is released via the regulated secretory pathway. Generation and analysis of knockout mice that fail to synthesize VGF indicate that this protein plays a critical, non-redundant role in the regulation of energy homeostasis, providing a possible link between neurotrophin function in the nervous system and the peripheral control of feeding and metabolic activity. Future experiments should clarify the sites and mechanisms of action of this neurotrophin-regulated neuronal and neuroendocrine protein.
 ...
PMID:Neurotrophins, growth-factor-regulated genes and the control of energy balance. 1263 1


1 2 3 Next >>