Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus (original) (raw)
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Seizure-induced gene expression in area CA1 of the mouse hippocampus
European Journal of Neuroscience, 2001
Synaptic plasticity in the hippocampus requires activity-dependent gene expression. We have therefore pro®led gene expression in area CA1 following the induction of an electroshock-evoked maximal seizure. Using cDNA microarrays, the differential expression of » 9000 cDNAs was examined. In situ hybridization on 14 transcripts that showed strongest modulation in the microarray screen (1.8±2-fold) con®rmed the differential expression of a single gene that encodes for the nuclear hormone receptor NGFI-B (Nur77, N10). Although this gene is only modestly up-regulated (» 2-fold) in area CA1, in situ hybridization revealed that maximal seizures induce a marked (» 12-fold) up-regulation of NGFI-B in the dentate gyrus. These data support the notion Eur. J. Neurosci., 13, 968±976] that CA1 pyramidal neurons are more refractory than granule cells of the dentate gyrus with respect to activity-dependent gene transcription. Furthermore, our results argue against a large cohort of activity-dependent genes in area CA1.
Seizures increase basic fibroblast growth factor mRNA in adult rat forebrain neurons and glia
Molecular Brain Research, 1994
The distribution of basic fibroblast growth factor (bFGF) mRNA in normal rat forebrain, and the influence of recurrent seizure activity on the expression of this mRNA, was evaluated using in situ hybridization and S1 nuclease protection techniques. In the untreated adult rat. hybridization of 35S-labeled bFGF cRNA densely labeled neurons in a few discrete areas including the tenia tecta, indusium gresmm, and hippocampal stratum pyramidale of regions CA2 and rostromedial CA1. Neurons in the prosubiculum and rostromedial dentate gyrus stratum granulosum were lightly labeled. In addition, a diffuse distribution of autoradiographic labeling in areas such as the hippocampat molecular layers, olfactory cortical layer I, and the olfactory nerve layer was suggestive of localization in glial ceils. Platinum wire hilar lesions, which did not induce seizures, increased cRNA hybridization in glial cells in primary and secondary areas of degeneration in the ipsilateral hemisphere only; hybridization was not noticeably increased in neurons in these lesion-control rats. Focal stainless-steel wire hilar lesions, which caused recurrent seizures 2-10 h postlesion, induced bilaterally distributed increases in cRNA hybridization in hippocampus, neocortex, olfactory cortex. amygdala, and septum. These seizure-dependent increases in hybridization were evident 6 h postlesion, were maximal from 12 to 24 h postlesion, and declined to near control levels by 4 days. In most regions the elevated hybridization appeared to be associated primarily with astroglia but m experimental seizure rats sacrificed 12 and 24 h postlesion hybridization was also markedly increased in the dentate gyrus granule cells and olfactory cortical neurons. These results demonstrate that recurrent seizures increase bFGF mRNA expression by both forebrain neurons and glia and implicate bFGF in the coordination of other changes in the biosynthetic activities of forebrain neurons that occur after seizures.
Neuroscience, 1993
Basic fibroblast growth factor promotes the survival and outgrowth of neurons and protects neurons from glutamate mediated excitotoxicity. The present study investigates the effects of kainate-induced epileptic seizures on the cellular expression of basic fibroblast growth factor messenger RNA and protein. Seizures were induced by injection of 12 mg/kg kainic acid. Rats were killed 3 h, 6 h, and 24 h after injection of the drug and analysed by radioactive and non-radioactive in situ hybridization as well as immunohistochemistry for glial fibrillary acidic protein and basic fibroblast growth factor. Radioactive in situ hybridization revealed a fast (6 h), strong (300-400% of control) and widespread increase of basic fibroblast growth factor messenger RNA after kainate-induced seizures. Non-radioactive in situ hybridization using digoxigenin-labeled riboprobes combined with glial fibrillary acidic protein immunohistochemistry showed that basic fibroblast growth factor messenger RNA wa...
European Journal …, 2010
We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected and contralateral hippocampus participated in the status epilepticus. However, neuronal death induced by KA treatment was restricted to the injected hippocampus, although there was some contralateral axonal degeneration. We profiled gene expression changes in dorsal and ventral regions of both the injected and contralateral hippocampus. Changes were detected in the expression of 1526 transcripts in samples from three time-points: (i) during the KA-induced status epilepticus, (ii) at 2 weeks, before recurrent seizures emerged, and (iii) at 6 months after seizures emerged. Grouping genes with similar spatio-temporal changes revealed an early transcriptional response, strong immune, cell death and growth responses at 2 weeks and an activation of immune and extracellular matrix genes persisting at 6 months. Immunostaining for proteins coded by genes identified from array studies provided evidence for gliogenesis and suggested that the proteoglycan biglycan is synthesized by astrocytes and contributes to a glial scar. Gene changes at 6 months after KA injection were largely restricted to tissue from the injection site. This suggests that either recurrent seizures might depend on maintained processes including immune responses and changes in extracellular matrix proteins near the injection site or alternatively might result from processes, such as growth, distant from the injection site and terminated while seizures are maintained.© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
2000
In adult brain, nerve growth factor (NGF) gene expression is generally upregulated by neuronal activity. However, a single episode of hilus lesion (HL)-induced limbic seizures stimulates a biphasic increase in NGF mRNA expression with peaks at 4-6 and 24 hr after lesion and an intervening return to control levels at 10-12 hr after lesion. In vitro studies suggest that NGF transcription is regulated via an activating protein 1 (AP-1) binding site in the first intron of the NGF gene. To examine the relationship between seizure-induced AP-1 binding and NGF gene expression in this paradigm, NGF mRNA levels and AP-1 binding were examined after HL seizures. Furthermore, to gain insight into the functional composition of the AP-1 complex, supershift analysis was performed to characterize which Fos and Jun family members are included in the AP-1-binding complex at the different time points analyzed. Solution hybrid-ization analysis verified the biphasic increase in NGF mRNA content of the dentate gyrus after HL seizures. After an initial increase, AP-1 binding slowly declined in a stepwise manner that encompassed, but did not correspond with, the two phases of NGF mRNA expression. However, supershift analyses demonstrated that the relative contributions of JunD and JunB to the AP-1 complex exhibited positive and negative correlations, respectively, with the phases of increased NGF expression after HL. These results suggest that AP-1 complexes containing JunD promote NGF transactivation and that transient changes in the relative contributions of JunD and JunB to AP-1 binding underlie the biphasic increase in NGF gene expression induced by HL seizures.
Journal of Neurochemistry, 2002
Previous studies have indicated that increased formation of oxygen free radicals is likely to participate in the cascade of events leading to neuronal damage following kainic acid (KA)-induced seizure activity. As reactive oxygen species are involved in signal transduction pathways leading to nuclear factor-KB (NF-KB) activation, we examined the effects of KA treatment on the activation of NF-KB in adult and juvenile rat brain. For comparison, changes in two other transcription factors, activator protein-i (AP-i) and Spi, were also determined. In adult rat piriform cortex and hippocampus, significant induction of NF-KB was observed at 4 h after KA injection, and the maximal increase was reached at 8-16 h posttreatment. NF-KB binding activities returned to control levels by 5 days after injection. NF-KB binding activities were slightly decreased in adult rat cerebellum at 8 and 16 h after KA treatment. In the juvenile rat, no significant changes in NF-KB binding activity were observed in piriform cortex, hippocampus, and cerebellum after KA injection. Changes in AP-i binding activity were qualitatively similar to those observed with NF-KB in adult but not juvenile rat brain, as AP-i was significantly induced in juvenile piriform cortex and hippocampus following KA injection. On the other hand, little or no changes in Spi activity were detected in adult and juvenile rat brain. Our results provide further evidence that oxidative stress participates in neuronal damage resulting from KA-induced seizure activity.
Long-term increase of Sp-1 transcription factors in the hippocampus after kainic acid treatment
Molecular Brain Research, 1999
Systemic administration of kainic acid KA , a glutamate receptor agonist, causes robust seizures and has been used as an excellent rodent model for human temporal lobe epilepsy. Recently, we have demonstrated that a single injection of KA increases the steady-state Ž . levels of proenkephalin PENK mRNA in the rat hippocampus for at least one year. However, the molecular mechanisms underlying this long-term increase in PENK mRNA levels have not been clearly defined. To determine the possible involvement of the Sp-1 transcription factors in this regulation, electrophoresis mobility-shift assays were used to study the expression of Sp-1 factors in the hippocampus after KA treatment. The results showed that there are long-lasting increases in Sp-1 DNA-binding activity. The Sp-1 DNA-binding complexes were only competed by the non-radioactive Sp-1 element and not by ENKCRE2, AP-1 or CRE elements, indicating the specificity of Sp-1 DNA-binding activity. Since the expression of Sp-1 parallels the time course of long-lasting increase in the expression of PENK mRNA and mossy fiber sprouting after KA treatment, we hypothesize that the increase in Sp-1 activity may be associated with the long-term changes in the plasticity of hippocampal function after KA-induced seizures. q
Levels of mRNA for a putative kainate receptor are affected by seizures
Proceedings of the National Academy of Sciences, 1990
In situ hybridization and RNA blot-hybridization techniques were used (i) to exmine the regional distribution of mRNA for a putative kainate receptor in adult rat brain and (i) to test the possibility that seizures affect expression of the receptor gene. The highest densities of hybridization were distributed within hippocampal pyramidal and granule cells, medial habenula, Purkiqje cells and the molecular layer of cerebellum, and olfactory bulb. Recurrent limbic seizures caused a massive,