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W Tischmeyer

Publications and source records attributed to W Tischmeyer.

13 recordsLinked to original sources
PubMed2001

Kainate-induced seizures alter protein composition and N-methyl-D-aspartate receptor function of rat forebrain postsynaptic densities.

The postsynaptic density is a highly dynamic structure, which is reorganized in an activity-dependent manner. An animal model for temporal lobe epilepsy, i.e. kainate-induced limbic seizures in rats, was used to study changes in postsynaptic density composition after extensive synaptic activity. Six hours after kainate injection, the protein content of the postsynaptic density fractions from rats that developed strong seizures was increased three-fold compared to saline-treated controls. Immunoblot analysis revealed that the relative amounts of metabotropic glutamate receptor 1alpha, N-ethylmaleimide-sensitive fusion protein, protein kinases C, Fyn and TrkB, as well as the neuronal nitric oxide synthase, were significantly higher in seizure-developing than in control rats. In contrast, the relative contents of the kainate receptor KA2 subunit, beta-actin, alpha-adducin and the membrane-associated guanylate kinase homolog SAP90/PSD-95 were decreased. The relative amounts of additional postsynaptic density proteins, including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate receptor subunits, calcium/calmodulin-dependent kinase type II, casein kinase 2, tubulin, microtubule-associated protein 2B, the membrane-associated guanylate kinase homolog SAP102, and proline-rich synapse-associated protein 1/cortactin binding protein 1/Shank2 remained essentially unchanged. To assess possible changes in postsynaptic performance, postsynaptic densities were isolated from control and epileptic rats, incorporated into giant liposomes and N-methyl-D-aspartate receptor currents were recorded. A significant reduction in the mean conductance was observed in patches containing postsynaptic densities from animals with high seizure activity. This was due to the presence of reduced conductance levels in each membrane patch compared to control postsynaptic density preparations. From these data, we suggest that intense synaptic activity associated with seizures modifies the composition of postsynaptic densities and has profound consequences on the function of the N-methyl-D-aspartate receptors present in them. This rearrangement may accompany impairment of synaptic plasticity.

Animals↗
PubMed1999

Co-expression of c-Jun and ATF-2 characterizes the surviving retinal ganglion cells which maintain axonal connections after partial optic nerve injury.

The expression of c-fos, c-jun, jun-b, jun-d, srf and pc4 mRNA was examined after partial optic nerve crush in the adult rat retina by in situ hybridization. Optic nerve injury led exclusively to the upregulation of c-jun, with cellular label indicative for c-jun mRNA in the retinal ganglion cell layer after two days, three days and one week post-injury. This expression pattern was in accordance with the appearance of c-Jun immunoreactivity in retinal flat mounts. Injection of an antisense but not a missense oligonucleotide against c-jun after partial crush resulted in a reduced number of connected retinal ganglion cells (RGCs) as shown by retrograde labeling. Prelabeling of RGCs with fluorogold before optic nerve section and subsequent antisense targeting against c-jun, however, led to a slightly higher number of surviving but axotomized RGCs. C-Jun antibody staining of retinal whole mounts pre- or postlabeled after crush by intracollicular administration of fluorogold showed strong c-Jun immunoreactivity in connected RGCs and also in a population of disconnected RGCs. Double labeling with an antibody directed against the transcription factor ATF-2 revealed strong co-expression of c-Jun and ATF-2 in connected RGCs but not in axotomized cells. Taken together these data indicate that both RGCs in continuity and those in discontinuity with the superior colliculus respond both equally to the noxious stimulus with c-Jun expression. Moreover, the co-expression of c-Jun with high levels of ATF-2 appears to be essential for either the continuity or survival of RGCs which remain connected with their target. In disconnected RGCs, however, low levels of ATF-2 and the co-expression of c-Jun may be related to cell death.

Activating Transcription Factor 2↗
PubMed1999

Activation of immediate early genes and memory formation.

Long-term plastic changes in the brain, including those supporting memory formation, are assumed to depend on permanent functional alterations in neuronal cells that require reprogramming of gene expression. Inducible transcription factors encoded by immediate early genes such as c-fos, c-jun, jun-B and zif/268 (also known as krox-24, egr-1, TIS 8, NGFI-A or zenk) are supposed to act as messengers in coupling short-term neuronal activity with changes at the level of gene transcription. This review will summarize studies on the expression of transcription factor-encoding immediate early genes in the vertebrate brain during behavioral training. Special emphasis will be given to correlative or interventive experimental evidence indicative of a physiological significance of inducible transcription factors for processes underlying learning and memory formation.

Animals↗
PubMed1998

BrainView: a computer program for reconstruction and interactive visualization of 3D data sets.

A computer program, BrainView, is presented which has been developed to reconstruct, visualize, and evaluate three dimensional (3D) biological and medical imaging data, such as images from histological sections, confocal microscopy, or magnetic resonance tomography. The program allows the simultaneous display of three orthogonal sectional planes, i.e. the horizontal, frontal, and sagittal planes, of reconstructed data and to move interactively through the brain to optimally assess the 3D data set. Furthermore, any arbitrary sectioning plane through a data set can be visualized. Implemented warping algorithms allow the geometric normalization of data sets of different animals, modalities or developmental stages as a preprocessing for the comparative evaluation of the data. For a quantitative analysis, data sets can be segmented based on equal grey levels and the corresponding equidensities were calculated. The program works on Apple-Macintosh computers and has a user-friendly graphical interface. The BrainView program is discussed in comparison to related programs.

Animals↗
PubMed1997

Complex patterns of immediate early gene induction in rat brain following brightness discrimination training and pseudotraining.

Following training of rats on a footshock-motivated brightness discrimination task in a Y-maze, different sets of transcription factor encoding immediate early genes (IEGs) were induced in anatomically distinct brain regions. As revealed by Northern analysis, mRNA levels of c-fos, jun-B and zif/268 increased in the hippocampus, while the expression of c-jun remained unchanged over a period of 7 h. In the cerebral cortex, c-jun was induced in addition to the other genes examined. In contrast, only c-fos, but not c-jun or zif/268 mRNAs were increased in the cerebellum. The induction of IEGs was rapid and transient, reaching maximal levels immediately after training and returning to basal levels within 2 h. Similar spatiotemporal expression patterns were observed in rats that received identical, but unpaired, stimuli in a pseudotraining procedure. Our results suggest that the initial prerequisites of learning, such as stimulus novelty, lead to an increased expression of IEG mRNAs after training and pseudotraining as an early necessary but not sufficient precondition for memory consolidation. Additional converging inputs might control at the transcriptional, translational or post-translational level the synthesis and biological effectiveness of proteins necessary to complete the formation of the memory trace in trained animals.

Animals↗
PubMed1996

Patterns of nitric oxide synthase at the messenger RNA and protein levels during early rat brain development.

There is substantial evidence that the intra- and intercellular messenger nitric oxide, generated enzymatically from L-arginine by nitric oxide synthase in different isoforms, is involved in the development of nervous tissue. In this study we investigated the nitric oxide expression in the pre- and postnatally developing rat brain. With regard to messenger RNA, all of the basic nitric oxide synthase isoforms (neuronal, endothelial and macrophage nitric oxide synthase) were already expressed at embryonic day 10 and showed a temporary decrease at embryonic day 17. Western blot analysis of the three isoform proteins revealed a time pattern that was different from those of messenger RNAs. Although the endothelial nitric oxide synthase isoform was also expressed at embryonic day 10, no quantitative changes were observed over the whole time period studied. Protein amounts of brain and inducible nitric oxide synthase were first detectable at embryonic day 15, with a tendency to rise. A parallel time pattern was found for the NADPH-diaphorase activity in our light microscopic studies, whereas ultrastructurally the reaction product was seen in the brain pallium even of 13-day-old embryos. The data indicate a permanent presence of the transcripts for all nitric oxide synthase isoforms in the rat central nervous system from embryonic day 10 onwards, although the expression of respective proteins and staining patterns may differ.

Aging↗
PubMed1994

Sequence-specific impairment of learning by c-jun antisense oligonucleotides.

Hybridization studies revealed a differential accumulation of c-jun and jun B mRNA in the hippocampus and cerebral cortex of rats trained on a foot-shock-motivated brightness discrimination. Supposing that early gene expression is functionally significant for plastic changes in the brain, we used antisense phosphorothioate oligodeoxynucleotides (S-ODN) in vivo to study effects of specific inhibition of c-jun and jun B gene expression on learning and memory formation in rat brain. Discrimination performance of rats was impaired after intrahippocampal injection of anti-c-jun S-ODN but not of anti-jun B S-ODN. These results imply that topically injected antisense oligonucleotides affect processes involved in learning and memory in a sequence-specific manner.

Animals↗
PubMed1992

Induction of expression of genes encoding transcription factors in the rat brain elicited by behavioral training.

c-fos and zif/268 are regulatory genes encoding transcription factors able to influence gene expression directly. It has been shown repeatedly that expression of transcription factors correlates with different forms of cell activation, probably being functionally involved in the coupling of extracellular signals with long-term cellular responses. This study describes that c-fos and zif/268 mRNA accumulation, as measured by northern blot analysis, occurs in the rat hippocampus as well as the visual cortex following behavioral training of two-way active avoidance response.

Animals↗
PubMed1991

c-fos protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path.

The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c-fos expression in both hippocampus and entorhinal cortex, and the increase of c-fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy.

Animals↗
PubMed1990

Accumulation of c-fos mRNA in rat hippocampus during acquisition of a brightness discrimination.

Training rats to attain a foot-shock-motivated brightness discrimination in a Y-maze results in an early and transient increase of hippocampal c-fos mRNA levels. Maximal accumulation was observed immediately after training, returning to basal levels during the following 2 h. A similar increase was obtained when rats were subjected to a pseudotraining with an equal number of runs, but with random pairing of the choice of bright and dark alleys with foot shock. It is suggested that induction of hippocampal c-fos mRNA expression is a necessary, but not sufficient, prerequisite for the formation of long-term memory trace. This early gene expression seems rather to correspond to an initial stage induced by complex stimulus presentation of both the training and the pseudotraining procedure. The subsequent late synthesis or processing of target proteins finally contributing to the formation of a permanent trace requires the action of further convergent signals to principal cells, probably mediating reward or emotional influences.

Animals↗
PubMed1990

Metabolization of a retention-improving dosage of methylglucamine orotate in rat brain.

The present study was carried out to investigate the time course of metabolization in brain and the influence on RNA synthesis of a retention-improving dosage of methylglucamine orotate after intracerebroventricular application. As determined by the HPLC technique, 73% of acid-soluble radioactivity were recovered in unmetabolized orotic acid 30 min after injection of 1 mumole methylglucamine [6-14C]orotate. Two hours later the amount of radioactivity found in this compound was negligible. Analysis of the sequence of labelling of uridine compounds revealed uridine to be the metabolite exhibiting the highest radioactivity at 30 min, whereas UMP- and UDP-sugars attained their maximum 90 min after injection of the precursor. Incorporation of [3H] guanosine into brain RNA was not altered by intraventricular application of 1 mumole methylglucamine orotate as compared to methylglucamine chloride-treated controls. The results are interpreted in the light of behavioural findings in which the pyrimidine nucleotide precursor at the dosage used improved the retention performance of an acquired behaviour in the rat.

Animals↗
PubMedDate not supplied

Suppression of c-fos induction in rat brain impairs retention of a brightness discrimination reaction.

Recently, the induction of transcription factor-encoding immediate-early genes such as c-fos was observed in distinct brain regions of rats trained to acquire a footshock-motivated brightness discrimination in a Y-maze. The functional relevance of inducible transcription factors for learning and memory formation is, however, not clear. To address this question in the present study, we have used a synthetic antisense phosphorothioate oligodeoxynucleotide to suppress in vivo the expression of c-fos in rat brain. Intrahippocampal application of the oligodeoxynucleotide 10 hr and 2 hr before starting a brightness discrimination training drastically reduced the induction of c-Fos immunoreactivity normally observed in limbic and cortical areas after the training session. Acquisition of the discrimination reaction was not affected by this treatment. In a relearning test 24 hr after the first training, retention of the discrimination reaction was specifically impaired compared with rats pretreated with control oligodeoxynucleotide or saline. Our findings are consistent with the hypothesis that the inducible transcription factor c-Fos is involved in processes underlying the formation of long-term memory.

Animals↗