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

Immunocytochemistry with specific antisera was used to assess regional levels of six immediate early gene encoded proteins (KROX-24, c-FOS, FOS B, c-JUN, JUN B and JUN D) in the rat hippocampus after 15 min of bicuculline-induced seizures. Serial sections of the dorsal hippocampus were examined at various postictal recovery periods up to 24 h. The results demonstrate a complex temporal and spatial pattern of immediate early gene synthesis and accumulation. Three major categories of immediate early gene products could best be distinguished in the dentate gyrus: KROX-24 and c-FOS showed a concurrent rapid rise with peak levels at 2 h and a return to baseline levels within 8 h after seizure termination. FOS B, c-JUN and JUN B levels increased more gradually with peak intensities in the dentate gyrus reached at 4 h. These immediate early gene products showed above normal levels in various hippocampal subpopulations up to 24 h. JUN D exhibited the most delayed onset combined with a prolonged increase of seizure-induced immunoreactivity. Irrespective of this differential temporal expression profile of individual transcription factors, the sequence of induction in the hippocampal subpopulations was identical for all immediate early gene-encoded proteins examined: first in the dentate gyrus granule cells followed by CA1 and CA3 neurons, respectively. Our data indicate an asynchronous synthesis of several immediate early gene-encoded proteins in the brain after status epilepticus. FOS and JUN proteins act via homo- or heterodimer complexes at the AP-1 and other DNA binding sites. The different time-courses for individual immediate early gene products strongly suggest, that at different time-points after status epilepticus, different AP-1 complexes are effective. In vitro studies have shown that different AP-1 complexes possess different DNA binding affinities as well as different transcriptional regulatory effects. Our results suggest that these molecular mechanisms are also effective in vivo.
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PMID:Induction of immediate early gene encoded proteins in the rat hippocampus after bicuculline-induced seizures: differential expression of KROX-24, FOS and JUN proteins. 160 23

The mechanism(s) by which long-term changes are induced and maintained in the nervous system are poorly understood. Kindling is an example of a permanent change in brain function that results from repeated elicitation of seizures. Recently, a class of genes called "immediate-early genes" that were previously thought to be only involved in cell division, differentiation and perhaps neoplasia have been shown to be rapidly and transiently induced in adult neurons following afterdischarges, ECS and chemically-evoked seizures. The products of these genes (e.g., FOS, JUN) are DNA-binding proteins and it is thought that they alter, perhaps in a coordinate fashion, the transcription of "late-effector genes." These late genes may code for enzymes, neuropeptides, receptors, ion channels, structural proteins, growth factors, etc. that may cause permanent biochemical and/or morphological changes in the brain that give rise to the kindled state. Thus, these early genes may act as molecular switches turning on a plasticity (kindling) program in neurons in a fashion similar to their induction of developmental programs in dividing cells.
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PMID:Immediate-early genes, kindling and long-term potentiation. 269 35

During the development of the CNS, a salient issue is whether neuronal phenotype is defined by the lineage or by the environment of precursor cells. Transplants permit these two possibilities to be tested, as cell fate can be examined in a new location. Dissociated cerebellar cells from newborn rats treated with tritiated thymidine or from NSE-lacZ transgenic mice were grafted into the dentate gyrus of the developing hippocampus. Implanted cells integrated into the granule cell layer, which contains the cell bodies of host granule neurons. Immunohistochemistry showed that grafted cells in the granule cell layer, like the host hippocampal granule neurons, were calbindin positive and upregulated FOS in a seizure paradigm. Electron microscopic analysis also showed that cells grafted to the dentate gyrus share features with host dentate neurons. These assays indicate that transplanted cerebellar cells acquired morphological and antigenic features characteristic of hippocampal neurons. These results show that metencephalic precursors are capable of differentiating in response to signals in the telencephalon, suggesting that the environment controls the regional fate of neuronal precursor cells during neurogenesis.
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PMID:Cerebellar precursors transplanted to the neonatal dentate gyrus express features characteristic of hippocampal neurons. 747

The present study examined the response of immediate early genes following kainic acid induced seizures in mice lacking the alpha and delta isoforms of CREB. mRNA levels for c-fos, c-jun, and Krox-24 were measured following limbic seizure activity and were found to be induced in wild type as well as CREB mutant mice. This effect was also seen for these three mRNAs at the protein level as well as for FOS-B. Furthermore the time course of expression of FOS, JUN, KROX-24, and FOS-B proteins were essentially the same in CREB mutant mice as compared to wild-type controls. These data suggest that CREB alpha and delta are not required for the induction of immediate early genes following pharmacologically induced seizures.
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PMID:Effects of kainic acid induced seizures on immediate early gene expression in mice with a targeted mutation of the CREB gene. 755 95

Cortical primordia of rat fetuses (gestation day 14) were stereotactically grafted into the rostral striatum of adult recipient rats. After 8 weeks, the transplants had developed into a highly differentiated population of mature neuroectodermal cells. Host rats were then subjected to 15 min of bicuculline-induced epileptic seizures or served as controls. Seizure-elicited immediate early gene (IEG) expression was investigated after various postictal survival times (up to 24 h), using immunocytochemistry with specific antisera against seven IEG encoded proteins (c-FOS, FOS B, c-JUN, JUN B, JUN D, KROX-24, KROX-20). Constitutive IEG expression in intra striatum grafted neocortical neurons was identical to that in the corresponding host neocortex. In particular, abundant KROX-24 and lack of c-JUN expression implies the establishment of synaptic contacts within the graft or with the host circuitry. Postictal expression kinetics of individual IEG encoded proteins within the transplants were strikingly similar to those seen in the neocortex in situ. c-FOS and KROX-24 were most rapidly induced, followed by c-JUN and JUN B, and a more delayed induction of FOS B, JUN D and KROX-20. Apart from a slightly prolonged c-FOS expression in grafts, individual transcription factors remained elevated for different time periods and showed a concurrent decline in transplants and in neocortex in situ. In conclusion, IEG induction in grafts closely paralleled that in the host neocortex but differed from the adjacent striatum which exhibited no c-JUN induction at any time point investigated. These results indicate that following an appropriate differentiation period, heterotopically grafted embryonic cortical neurons respond to extracellular stimuli with changes of gene expression that closely resemble the normal host cortex. This suggests development of a similar molecular phenotype, including proper acquisition and intracellular processing of information.
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PMID:Concurrent immediate early gene induction by epileptic seizures in heterotopic cortical grafts and neocortex. 801 98

In microdialysis procedures high potassium ion concentrations are generally used to induce neurotransmitter release. However, the widespread effects, if any, of such a treatment have not been described. In order to establish a possible link between c-fos expression and stimulating conditions for neurotransmitter release in microdialysis procedures we administered KCl (100 mM) into the hippocampus. Proto-oncogene c-FOS-like immunoreactivity is upregulated in granule cells of the dentate gyrus, pyramidal cells of the hippocampus, cingulate, piriform and frontoparietal cortices at 2 h, but not 24 h after K+ administration. Neither implantation of the probes nor perfusion with artificial cerebrospinal fluid resulted in similar patterns of c-FOS immunoreactivity. In addition, we investigated whether the impairment of the cholinergic septohippocampal pathway would modify the K(+)-induced expression of the immediate early gene c-fos in the hippocampus. The expression of c-fos induced by KCl was not altered in the animals with fimbria-fornix lesion despite the marked decrease in acetylcholine release in the hippocampus. Glutamate concentrations measured in the same superfusates showed that a significantly greater glutamate release occurs in denervated hippocampi. Furthermore, abolishment of seizure-like activity (induced by KCl) in anesthetized animals did not alter expression of c-FOS immunoreactivity in the K(+)-stimulated hippocampi. The results from these studies confirm that most of the releasable acetylcholine of the hippocampus is linked to the fimbrial input and may suggest that c-FOS upregulation in this model does not respond to any cholinergic input from the medial septum via the fimbria-fornix.
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PMID:Induction of c-FOS immunoreactivity in the hippocampus following potassium stimulation. 809 2

The expression of the nuclear c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB transcription factors was investigated in the cortex of adult rats by immunocytochemistry. The expression patterns were studied in untreated rats and up to 24 hours following topical application of 1 M KCl to the cortical surface (KCl) or i.v. injection of bicuculline (BIC). Topical KCl induced cortical spreading depression and systemic injection of bicuculline evoked generalized tonic-clonic seizures. In untreated rats, JUN B, c-FOS, and FOS B were expressed in a small number of neurons in the piriform, perirhinal, entorhinal, and insular cortex and in layers II, III, and VI of all neocortical areas. In contrast, c-JUN, JUN D, and KROX-24 were expressed in all cortical layers but with different intensities of immunoreactivity (IR): c-JUN-IR was generally weak and predominantly present in layers II, III, and VI. JUN D-IR was equally strong in all layers. KROX-24 showed a prominent expression in layers II, IV, and VI. The CREB protein exhibited a slight preponderance in layer II and piriform cortex. Following KCl or BIC, a strong induction was seen for c-FOS, JUN B, and KROX-24, whereas c-JUN, JUN D, and FOS B showed only a moderate increase compared to basal levels. Changes of CREB-IR could not be detected. The localization of induced JUN, FOS, and KROX proteins reflected the pattern of labelling in untreated animals but demonstrated a higher intensity of labelling and an increased number of immunoreactive nuclei. The intensity and persistence of IR as well as the number of labelled cells following BIC exceeded those following KCl. Following BIC, increased levels of FOS B and JUN D were still present after 24 hours. Counterstaining with cresyl-violet and GFAP, a marker for astrocytes, revealed that JUN, FOS, and KROX proteins were expressed in neurons but not in glial cell populations. The present data demonstrate that CREB, JUN, FOS, and KROX transcription factors exhibit a layer-specific expression in the cerebral cortex with only slight area-specific differences both in untreated rats and following stimulation with KCl and BIC. The expression of transcription factor proteins indicate complex molecular genetic changes in cortical neurons due to pathophysiological events such as seizure activity and spreading depression.
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PMID:JUN, FOS, KROX, and CREB transcription factor proteins in the rat cortex: basal expression and induction by spreading depression and epileptic seizures. 834 7

The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.
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PMID:Expression of c-fos protein in the experimental epilepsy induced by pilocarpine. 851 14

Previous studies have shown the successive expression of c-fos and hsp70 genes, especially in the hippocampal formation, during soman-induced seizures. In order to detect a possible link between the induction of these two genes, antisense strategies have been used. First, the ability of unilateral intrahippocampal infusion of c-fos antisense oligonucleotides to inhibit ipsilateral, seizure-related, c-FOS-like immunoreactivity, was verified. Second, induction of hsp70 mRNA was investigated using in situ hybridization. Unilateral inhibition of c-fos induction clearly reduced levels of hsp70 mRNA in the c-fos antisense-infused hippocampus relative to the non-infused contralateral side. Infusion of c-fos sense probe or vehicle did not affect bsp70 mRNA induction. This study suggests a role of c-FOS in regulating bsp70 mRNA induction.
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PMID:c-fos antisense oligonucleotide prevents delayed induction of hsp70 mRNA after soman-induced seizures. 922 58

In the current study we employed immunohistochemical techniques to identify neuronal and glial cells in specific brain areas that modulate beta-amyloid precursor protein (betaAPP) synthesis following kainate-induced seizures. In addition, antibodies directed against the FOS protein, which is generated by activation of the immediate early gene c-fos and is temporally associated with ongoing seizure activity, were used to identify transneuronal pathways activated after kainate-induced seizures (KIS). It was therefore possible to correlate the appearance of activated neuronal pathways identified by FOS-like immunoreactivity (LI) and PAPP-LI in alternate sections. In addition, we employed immunohistochemical procedures to characterize morphological changes in neuronal and glial cells following kainate-induced seizures in both young and adult rats. Our results demonstrate a specific pattern of FOS-LI induced by kainate injection. In older animals FOS-LI spreads out from limbic cortical regions, including the piriform and entorhinal cortex, to other cortical regions, including the parietal and somatosensory cortices. Seizures were associated with decrease in neuronal betaAPP-LI in both young and adult rats, whereas glial betaAPP-LI markedly increased. The increase in betaAPP-LI glia was far more extensive in adult than in young rats and the anatomical distribution of betaAPP-LI glia was grossly correlated with FOS-LI. The spread of betaAPP-LI follows seizure-activated transsynaptic pathways. It is likely that the sequence of events following kainate injection is initially triggered by c-fos gene expression, which is rapidly followed by modulation of betaAPP synthesis in parallel to, or preceding, morphological changes of both microglia and astrocytes. The present study, which extensively characterized early changes in c-fos expression and betaAPP-LI in glia following kainate-induced seizures, is a potentially useful animal model for the in vivo study of numerous facets of betaAPP synthesis and the possible role of such processes in Alzheimer's disease.
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PMID:The distribution of beta-amyloid precursor protein in rat cortex after systemic kainate-induced seizures. 934 61


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