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M Krug

Publications and source records attributed to M Krug.

At least 55 records · Page 3Linked to original sources

Nerval influences on liver cytochrome P450.

In male young adult Wistar rats the influences of nucleus raphe electrocoagulation, spinal cord dissection (cordotomy between C7 and Th1), vagotomy and denervation of liver hilus by phenol on liver cytochrome P450-system (cytochrome P450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation activities, hexobarbitone sleeping time) were investigated. In general the influences were small or negligible when compared with sham operated controls, only after vagotomy the depressing effect of sham operation was abolished. In all cases sham operation had a depressing effect until up to five weeks after operation.

7-Alkoxycoumarin O-Dealkylase↗

Fucose and fucose-containing sugar epitopes enhance hippocampal long-term potentiation in the freely moving rat.

Male Wistar rats were intrahippocampally injected with L-fucose and the sugar epitope 2'-fucosyl-lactose prior to induction of long-term potentiation (LTP). Both substances had only a minimal and short-lasting depressive effect on the monosynaptically evoked field potential recorded in the dorsal blade of the dentate gyrus of freely moving rats upon stimulation of the perforant pathway. However, LTP induced by fractionated tetanization of the perforant pathway, which declined within 24 h in control animals injected with Lactose, remained at the initial level even 48 h after tetanization (difference to the control group significant with P < 0.01). The results support earlier findings which have indicated a participation of fucosylated macromolecules in the maintenance of LTP. Different molecular mechanisms concerning the effect of both substances and the significance of the data in elucidation of the relationship between LTP and memory formation are discussed.

Animals↗

Ileitis hyperplastica follicularis Golden: surgical or conservative treatment?

The authors report on four cases of Golden's syndrome, a rare disease with unknown etiology and controversial therapy. The first two 7-year-old boys had gastrointestinal bleeding; their hemoglobin levels were 7.0 g% and 7.3 g%, respectively. A blood transfusion was required. Both patients underwent gastroscopy and rectoscopy, and no source of bleeding was found. Biopsies were taken during laparotomy, after terminal ileotomy in case one and coecotomy in the other. Bowel resection was not necessary in either case. The third and fourth boys (5 and 6 years old, respectively) were treated conservatively with parenteral nutrition; blood transfusion was not necessary. All four patients recovered within several days. Control colonoscopies 6 months later showed normal mucosa. The authors discuss their diagnostic and therapeutical regime, stressing that in their experience, this rare disease does not require surgical intervention.

Child↗

Specific [3H]L-glutamate binding and [3H]D-aspartate release in the hippocampus of rat after pentylenetetrazol kindling and long-term potentiation.

In the present study, the time-course of changes in glutamate binding and aspartate release in the rat hippocampus following tetanization of perforant pathway and of pentylenetetrazol-induced kindling was investigated. The K+ (48 mM)-stimulated [3H]D-aspartate release from hippocampal slices and the specific [3H]L-glutamate binding to crude synaptic membranes of the hippocampus were measured 1, 4 and 24 h after the last tetanization train or one, five and nine weeks after the last pentylenetetrazol injections, respectively. The tetanization of the fascia dentata was followed by a significant increase in K(+)-stimulated [3H]D-aspartate release from hippocampal slices only 1 h after the last tetanization train, but the specific [3H]L-glutamate binding was enhanced 4 h afterwards. No further deviations from controls have been seen 24 h after tetanization. After pentylenetetrazol kindling, the K(+)-stimulated amino acid release from hippocampal slices was not changed. However, at one week as well as at five and nine weeks after the pentylenetetrazol kindling the specific [3H]L-glutamate binding in the hippocampus was significantly increased by about 50% compared to controls. From these findings it can be assumed that after long-term potentiation induction presynaptic transmitter release and post- (and/or pre-)synaptic glutamate binding are elevated with a different time course only in the early phase of potentiation. In contrast, kindling results in a long lasting increase in activity state of glutamatergic transmission. Therefore, it can be concluded that differences of the synaptic excitability following long-term potentiation and kindling are reflected by a different activation of glutamatergic system in the central nervous system.

Animals↗

Non-opioid antitussives and methadone differentially influence hippocampal long-term potentiation in freely moving rats.

Long-term potentiation (LTP) of monosynaptically evoked field potentials (MEFP) in the dentate gyrus of freely moving rats following tetanization of the perforant pathway was investigated after peripheral application of substances which have been shown to influence NMDA receptor-mediated effects (dextromethorphan, methadone) as well as structurally related substances with similar antitussive effects (codeine, normethadone). The noncompetitive NMDA receptor antagonist MK 801 was also tested for comparison. Whereas under control conditions the field e.p.s.p. (excitatory postsynaptic potential) and the population spike of the MEFP were largely uninfluenced by these substances, different effects were seen after the induction of LTP. MK 801 (0.2 mg/kg i.p.) suppressed the induction of LTP of both the field e.p.s.p. and the population spike. Dextromethorphan (40 mg/kg i.p.) also prevented the potentiation of the field e.p.s.p. and the population spike, thus resembling MK 801 in its effect. Codeine (20 mg/kg i.p.), the levorotatory structural analogue of dextromethorphan had no effect. Methadone and normethadone did not influence the potentiation of the field e.p.s.p. or interfere with the induction of potentiation of the population spike but depressed its maintenance. The results obtained with MK 801 confirm those reported by others. Comparison of the effects of dextromethorphan with those of MK 801, suggests that there is a direct interaction with the NMDA receptor-ionophore complex. The effects of methadone and normethadone appear not to be linked to an interaction with opioid receptors, since naloxone did not influence the suppression of LTP caused by methadone. The possibility of interference with the NMDA receptor-ionophore complex is discussed.

Animals↗

Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear diseases.

Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and IX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens II, IX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗

Do dentate area transplants take the function of damaged dentate area neurons in the rat brain after having replaced them?

Colchicine eliminates selectively dentata area granular cells after topical microinjections. In rats treated this way it was impossible to evoke field potentials by perforant parth stimulation and the animals were unable to learn if perforant path stimulation was used as conditioned signal. After colchicine lesion neonatal dentate area tissue was grafted into the lesioned region. Between 4 and 10 weeks after grafting it was again possible to evoke potentials after perforant path stimulation and the rats were able to learn, whereas colchicine-treated rats without grafts failed. The histological investigation showed well on grown neurons within the grafts. The grafts were well integrated. It was shown that the mossy fibers from the grafts innervated the deserted CA3 sector, and that the grafted neurons were innervated by nervous fibers from the recipient brain. It can be supposed that the granular cells from the grafts were able to taken the function of the damaged granular cells of the colchicine treated dentate area.

Animals↗

[Morphometric-stereological study of hippocampal long term potentiation with special consideration of the analysis of variance with two-way hierarchical classification].

Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of vesicles in axo-spino-dendritic synapses of the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. Between the 3 groups (passive control, active control, LTP-group) we found no significant differences. Because of the great differences between the vesicles even within a single synapse we subsequently investigated the middle third of the molecular layer, i.e. the terminal area of the stimulated perforant path. No differences between the three groups we found here either. There was no confirmation for the expected greater homogenization of the synapses based on the uniform input. As a result of this study pure morphological studies without selective staining of specific population of synapses are considered inadvisable. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.

Analysis of Variance↗

The influence of long-term potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain.

The influence of long-term potentiation (induced by repeated high-frequency stimulation of the perforant pathway) on the distribution pattern of astrocyte processes in the neuropil of the hippocampal dentate area containing the potentiated synapses was investigated by quantitative electronmicroscopy. It has been found that significant changes occurred in the ramification of astrocyte processes as well as in their topographic relation to synaptic complexes. When comparing the results obtained in LTP animals with active control or sham-operated animals, we found significant higher numerical density, but smaller volume, higher surface density and closer apposition of astrocyte processes to the synaptic clefts, boutons terminaux or spines in the potentiated synapses containing neuropil. The glial reaction to synaptic activation has been seen most pronounced 8 h after the LTP induction. The results are pointing to a participation of the glia cells in the maintenance of the LTP effect as well as to a metabolic coupling between synaptic transmission and glia function for equilibrating the homeostasis by clearing the extracellular space next to the transmission zones.

Animals↗

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↗

The amnesic substance 2-deoxy-D-galactose suppresses the maintenance of hippocampal LTP.

Male Wistar rats were intraventricularly injected with 2-deoxy-D-galactose (do-gal), a substance interfering with the fucosylation of glycomacromolecules and impairing memory consolidation in various learning tasks. Do-gal was found to have no influence on the monosynaptically evoked field potential (MEFP) recorded in the dentate gyrus upon stimulation of the perforant pathway. However, hippocampal long-term potentiation (LTP) induced in do-gal-pretreated animals by fractionated tetanization of the perforant pathway declined to control levels 2 h after tetanization, whereas it remained constant for 24 h in saline-treated rats. Similar effects were observed in the CA1 region of hippocampal slices. The results indicate a participation of fucosylated macromolecules in the maintenance of LTP. The possible significance of processes involved in LTP for memory formation is discussed.

Amnesia↗

ADAPTU: animated dynamics analysis program at Tübingen University.

Molecular dynamics calculations are being used more and more in computational chemistry to investigate inter- and intra-molecular properties, as well as to determine structures. Visualization of a calculated trajectory is needed to allow a detailed analysis of the huge amount of data generated by such calculations. In addition to animating trajectories, ADAPTU was written to permit diagram generation in two and three dimensions for a detailed analysis, the extraction and listing of properties of a selected conformation and the visualization of the development of constraints in a restrained dynamics. The displayed trajectory, as well as the three-dimensional (3D) diagrams can be scaled, translated and rotated, and displayed in cross stereo representation. Our graphics device is a E&S PS300 system, which is connected to a host by Ethernet or by an asynchronous line.

Anti-Bacterial Agents↗

Enhanced sensitivity of "metabotropic" glutamate receptors after induction of long-term potentiation in rat hippocampus.

Stimulation of [3H]inositol monophosphate ([3H]InsP) formation by ibotenate or trans-1-aminocyclopentyl-1,3-dicarboxylic acid (t-ACPD) in rat hippocampal slices was enhanced after tetanic stimulation of the Schaffer collaterals projecting to the CA1 region (in vitro) or the perforant pathway projecting to the dentate gyrus (in freely moving animals). This effect was observed 5 h (but not 2 h) after long-term potentiation (LTP) induction and was abolished if tetanic stimulation was performed in the presence of specific antagonists of N-methyl-D-aspartate receptors. The delayed increase in excitatory amino acid-induced polyphosphoinositide (PPI) hydrolysis was accompanied by an enhanced responsiveness to norepinephrine, whereas the basal and carbamylcholine-stimulated [3H]InsP formation were unchanged. These results suggest that an increased activity of "metabotropic" glutamate receptors may contribute to the synaptic mechanisms enabling the late expression and or maintenance of LTP. Accordingly, LTP decayed more rapidly (within 5 h) in rats repeatedly injected with LiCl (60-120 mg/kg, i.p., for 10 days), a treatment that led to a reduced efficacy of ibotenate and norepinephrine in stimulating PPI hydrolysis in hippocampal slices.

Animals↗

Heterosynaptic changes in number and shape of the transmission zones of axo-spino-dendritic synapses in the central nervous system following long-term potentiation.

Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of axo-spino-dendritic synapses from the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. We were looking for differences in the number of transmission zones, in the total length of the transmission zone and in the qualitative shape of the single transmission membrane. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. We detected large differences between the single synapses but not significant differences between the 3 groups (passive control, active control, LTP-group). Our quantitative studies showed the same results also in the middle third of the molecular layer (Grabs et al. 1991). Pure morphological studies should be done under selective staining of specified population of synapses to differ in stimulated and non-stimulated synapses. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.

Animals↗

Long-term potentiation induced changes in protein synthesis of hippocampal subfields of freely moving rats: time-course.

The incorporation of L-[U-14C]leucine into proteins of cytosolic (soluble proteins) and of the 100,000 x g pellet fraction from ipsilateral hippocampal subfields (CA1, CA3, CA4/area dentata) of rats was studied during and at various times after electrical tetanisation of the right perforant pathway using topical precursor applications and 1 h incorporation periods. Rates of protein synthesis were estimated calculating the relative specific radioactivity of proteins (RSA). The RSA-values of both protein fractions estimated in the ipsilateral CA4/area dentata were found to be about two times higher in tetanised rats compared to either passive or stimulated controls (p less than 0.05) when leucine was administered 5 min after tetanisation. Under these conditions, no differences between tetanised and control animals were observed in all other hippocampal subfields studied. No differences in RSA-values evaluated in CA4/area dentata between tetanised and passive controls were detected when leucine was administered immediately prior to tetanisation. From 2 h to 8 h after induction of LTP, protein synthesis in CA4/area dentata of tetanised rats appeared to be decreased (p less than 0.05) compared to passive controls. These results provide evidence for a transient LTP-induced augmentation of protein synthesis in the targets which might be an essential prerequisite for those structural changes realising the long-lasting enhanced efficacy of synaptic transmission at perforant path/granular cells connections.

Animals↗

Transient increase of raf protein kinase-like immunoreactivity in the rat dentate gyrus during long-term potentiation.

Altered levels of cellular raf proteins (products of the raf protooncogenes) have been shown in the neurons of the dentate fascia of rats in response to high-frequency stimulation, with light microscopic immunohistochemistry by using polyclonal antibodies. No raf-1-like staining was seen in unstimulated tissue, while the pan-raf antibodies revealed immunoreactivity in the cytoplasm of neurons in the Ammon's horn and dentate fascia of rats and guinea pigs. The induction of long-term potentiation in the dentate fascia of freely-moving rats triggered the appearance of raf-1-like staining and increased the number of granule cells with pan-raf-like immunoreactivity. Since these proteins are serine/threonine-specific protein kinases, their appearance in long-term potentiation may indicate the activation of important cell membrane - nucleus transduction pathways.

Animals↗

Spinules in axospinous synapses of the rat dentate gyrus: changes in density following long-term potentiation.

Following high frequency stimulation of the perforant path the density of axospinous synapses from the middle third of the molecular layer of the rat dentate gyrus did not change significantly. By contrast, within this synaptic population the density of axospinous synapses containing synaptic spinules increased markedly. We interpret these results in terms of a structural modification related to enhanced synaptic efficacy.

Animals↗