Different mechanisms and multiple stages of LTP.
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Animals↗
Biomedical subjects
M Krug
Publications and source records attributed to M Krug.
Posttetanic long-term potentiation in rat dentate area increases postsynaptic 411B immunoreactivity.
411B is a monoclonal antibody raised to chick forebrain postsynaptic densities (PSDs) which also recognises an antigen in brain tissue from adult Wistar rats but not liver, heart, or lung. This antigen is enriched in the PSD fraction and appears to be a useful biochemical marker for plastic changes of postsynaptic structures in the rat brain. The aim of this study was to investigate whether 411B immunoreactivity is changed in various hippocampal subregions by post-tetanic long-term potentiation (LTP). LTP was elicited in freely moving rats by applying four trains of 300 square-wave pulses (frequency 200 Hz, pulse duration 0.2 ms, and intensity 300 mA) into the right perforant path; this included an increase in transmission efficacy at the ipsilateral perforant path-granular cell synapse of the dentate gyrus lasting several days. Eight hours after tetanisation, antigens recognised by monoclonal 411B and a polyclonal anti-actin antiserum were assayed in lysed homogenates of ipsi- and contralateral CA1. CA3, and CA4/dentate area hippocampal subfields as well as in visual cortex, cerebellum, and olfactory bulb dissected from LTP rats, and compared to passive controls. Under these experimental conditions, tetanisation of the perforant path resulted in a significant increase in the titre of 411B in the ipsilateral CA4/dentate area subfield (+34.0%; p less than 0.001) compared with passive controls, whereas in all other brain regions studied no differences between experimental and control rats were observed. In no region were anti-actin titres significantly different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
Long-term potentiation and postconditioning potentiation--the same mechanism?
Stimulation of the perforant pathway with different stimulus pattern was used in freely moving rats to elicit classical posttetanic long-term potentiation (LTP), paired-pulse potentiation and postconditioning potentiation which appeared after using the perforant pathway stimulation as a conditioned stimulus in a shuttle-box learning paradigm. The changes in amplitude and latency of the population spike were compared. While in all experimental groups an amplitude potentiation of the population spike occurred, the changes in its latency were different. Only after inducing posttetanic LTP the latency decreased together with the amplitude increase. Postconditioning potentiation in good learners, however, was accompanied by a latency increase. In poor learners, on the other hand, a latency decrease immediately after the training session was the only change. Paired-pulse potentiation which occurred with an interstimulus interval of 50 ms, was also accompanied by a latency increase. The results indicate that the mechanism of learning-related potentiation cannot only be long-term potentiation. Even if assuming an involvement of LTP in the synaptic changes occurring after learning, it seems to be modified or overlapped by another alteration. Considering the similarity to observations after paired-pulse potentiation, a recruiting phenomenon can be assumed to contribute to these differences.
Animals↗
Posttetanic long-term potentiation in the dentate gyrus of freely moving rats is accompanied by an increase in protein synthesis.
In rats, the incorporation of L-[U-14C]leucine into proteins of cytosolic (soluble proteins) and of the 100,000 x g pellet fraction from ipsilateral hippocampus subregions (CA1, CA3 and CA4/area dentata) and visual cortex was studied from 5 min to 65 min after electrical tetanization of the right perforant path. The rates of protein synthesis were estimated calculating the relative specific radioactivity of proteins (RSA). The stimulation parameters used were identical to those of previous experiments inducing post-tetanic long-term potentiation (LTP) of both the amplitude of population spike and the slope function of the excitatory post-synaptic potential (EPSP) in the area dentata. Under these conditions, RSA-values of both fractions evaluated in the CA4/area dentata were found to be about two times higher in tetanized rats compared to either stimulated or passive controls (p less than 0.05). In all the other brain regions studied, no differences between tetanized and control animals were observed. These results provided evidence for an LTP-induced augmentation of protein synthesis in the ipsilateral dentate area which might be an essential prerequisite for those structural changes realizing the long-lasting enhanced efficacy of synaptic transmission at the perforant path-granular cell connections within this hippocampus subfield.
Animals↗
[Photodynamic therapy of bronchial cancer].
Photodynamic therapy (PDT) with porphyrin derivatives (haematoporphyrin and dihaematoporphyrin äther/ester) and laser light of the wavelength 640 nm, is a new procedure for the treatment of carcinomas. This form of therapy is selective, can be applied through the bronchoscope, and is aimed at accomplishing curative elimination of central tumours of the lung. To date, we have successfully applied PDT in four selected patients. Our first patient was treated in April, 1987. The irradiation modalities and the clinical course are described.
Adenocarcinoma↗
Methylglucamine orotate, a memory-improving drug, prolongs hippocampal long-term potentiation.
We showed earlier that the memory-improving substance, methylglucamine orotate, a precursor of pyrimidine nucleotide synthesis, improved memory retention and enhanced the postconditioning potentiation of field potentials in a special learning task. Since long-term potentiation (LTP) is frequently regarded as a mechanism of memory formation, we decided to test whether it can be influenced in a similar manner. The present study shows that the same dose of methylglucamine orotate (225 micrograms i.c.v.) prolongs LTP but has only a slight effect on the field potential recorded in the dentate gyrus. In controls, LTP of the population spike returned to 154% of the control value 24 h after tetanization and to 126% after 48 h. However, in drug treated animals LTP of the population spike remained at 246 and 216% of the control, respectively. The results support the assumption that LTP is at least a component of memory formation.
Animals↗
Long-term potentiation induced in dendrites separated from rat's CA1 pyramidal somata does not establish a late phase.
In 14 transversal hippocampal slices from rats the extracellular field-EPSP (excitatory postsynaptic potential) in the dendritic region of the CA1 subfield was recorded after isolating the apical dendrites from their somata by microsurgical cuts through the proximal stratum radiatum. Contrary to intact slices which, after tetanic stimulation of the Schaffer collaterals, showed long-term potentiation (LTP) until the end of registration after 8-10 h, LTP declined in the isolated dendrites to baseline values after 3 h. It is concluded that de-novo protein synthesis in postsynaptic cell bodies might be necessary for the maintenance of late phases of LTP.
Action Potentials↗
Habituation of monosynaptic field potentials in the dentate gyrus of freely moving rats interferes with LTP.
In 30 male Wistar rats, monosynaptically evoked field potentials in the dentate gyrus were registered under different conditions of repetitive stimulation and the long-term changes in synaptic transmission studied. Low-frequency stimulation induces a habituation-like decrement of the field-EPSP, but not of the population spike which interferes with the maintenance of LTP when administered after tetanic stimulation. The habituation-like response decrement, however, does not influence paired pulse-depression seen with an interstimulus interval of 20.0 ms. The paired pulse-plasticity, on the other hand, can be influenced by the tetanic stimulation (diminution of facilitation or depression), being dependent on the intensity of test stimuli. The results can be interpreted in terms of a complex influence of low-frequency- and tetanic stimulation on the elements of the dentate local circuitry and point to the necessity of considering long-term plastic changes in the investigation of substance- or stimulation-induced deviations of neuronal responses.
Action Potentials↗
Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.
A novel synthetic foot-and-mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B-cell and macrophage activator covalently linked to an amphiphilic alpha-helical T-cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-serine (P3CSS) as built-in adjuvant. The vaccine, tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl-FMDV-VP1 (VP1 = serotype O1K 135-154) induces protection against homologous challenge and serotype-specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV-VP1 segment 135-154 of strain O Wuppertal produced only poor cross-protection against challenge with O1K virus. The antigenic determinant VP1(135-154) is an amphiphilic alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-helical conformation during binding to its T-cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex.
Amino Acid Sequence↗
Bronchoscopic photodynamic therapy of bronchial carcinoma.
Photodynamic therapy with photosensitizers is a new method of treating malignant tumors. In the area of bronchoscopy it is employed for the selective therapy of early carcinomas at central localizations. We report on our first attempts at treatment with hematoporphyrin derivative in an inoperable patient. The modalities of irradiation and the recurrence-free progress of, to date, 2.5 years, are described.
Bronchoscopy↗
Orotate improves memory and enhances synaptic long-term potentiation in active avoidance behaviour in rats with perforant path stimulation as the conditioned stimulus.
Male Wistar rats were trained in an active avoidance task with stimulation of the perforant path with impulse trains of 15 Hz as the conditioning stimulus. Immediately after the first training session, methylglucamine orotate (225 micrograms), a memory improving drug, was injected intraventricularly. The retention of the learned behaviour was determined on the following day in a relearning session. Field potentials evoked in the dentate area by test stimuli from the perforant path electrode were recorded at different times after learning and relearning sessions to determine whether there were functional changes in the perforant path-granular cell synapses, which are involved in the conditioning pathway. Untreated control animals exhibited a so-called 'postconditioning potentiation', expressed as a long-lasting increase of both the excitatory postsynaptic potential (EPSP) and the population spike of the granular cells of the evoked test potentials. This finding reproduces previously published results. Methylglucamine orotate-treated rats showed significantly more conditioned reactions in the relearning sessions compared with untreated controls and a significantly more pronounced potentiation of the population spike, whereas the postconditioning potentiation of the field EPSP remained unaffected by the treatment. When both the control animals and the methylglucamine orotate-treated rats were divided into subgroups of good and poor learners according to their learning scores from the first training session, differences between the effect of the drug became evident. In good learners, the treatment with methylglucamine orotate after the learning session slightly, but significantly, improved retention compared with that of untreated good learners.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro.
Long-term potentiation (LTP) with its extremely long duration has been frequently regarded as an elementary mechanism of information storage in the nervous system or at least as a suitable model for the study of mechanisms underlying functional plasticity and processes of learning and memory formation. Considering the necessity of an increased protein synthesis for memory consolidation and for the maintenance of LTP in granular synapses in vivo it was of interest to determine whether the LTP of the CA1 region of the hippocampus depends on protein synthesis as well. For the solution of this question anisomycin (ANI), a reversible blocker of protein synthesis, was used at a concentration of 20 microM, which blocked the [3H]leucine incorporation in hippocampal slices by at least 85%. It has been shown that in the CA1 region in vitro the maintenance of LTP (i.e. a late phase greater than 5 h) depends on an ongoing protein synthesis. A 3-h treatment with ANI immediately following multiple tetanization resulted in gradually developing loss of field excitatory postsynaptic potential (EPSP) and population spike (PS) potentiation (15 +/- 19% increase of the PS instead of the 96 +/- 14% increase in non-treated control experiments at the 8th h after tetanization). Furthermore, a late PS potentiation (greater than 6 h) of a second non-tetanized pathway to CA1 pyramidal cells has been observed (increase by 64 +/- 18% at the 8th h) for the first time. This potentiation was ANI-sensitive as well and suggests that the maintenance of LTP is dependent on a postsynaptic mechanism.
Action Potentials↗
Incorporation of [3H]fucose in rat hippocampal structures after conditioning by perforant path stimulation and after LTP-producing tetanization.
The contribution of glycoprotein synthesis to functional synaptic changes and to the formation of memory traces was investigated by autoradiographic determination of the incorporation of [3H]fucose into the hippocampal structures of rats. In the first experiment, the fucose incorporation was measured after induction of post-tetanic long-term potentiation (LTP) in granular cell synapses by repeated tetanization (200 cps) of the perforant path, and after stimulation of this hippocampal input by the same number of impulses with very low frequency (0.2 cps) not producing LTP. In the second experiment, the incorporation of fucose was determined after an active avoidance training using the stimulation of the perforant path by impulse trains of 15 cps as conditioning stimuli, and after a session of corresponding unpaired stimulations of the perforant path. Unstimulated animals were used in both experiments to measure the basal glycosylation. LTP-producing tetanization resulted only in a slight increase of incorporation into the ipsilateral hippocampal structures without significant differences to similar changes after the corresponding control stimulation with single impulses. After a session of unpaired stimulation of the perforant path with impulse trains of 15 cps only slight and inconsistent changes of incorporation occurred in the hippocampus too. However, after conditioning by the corresponding perforant path stimulation as conditioned stimulus, considerable increases of incorporation were observed in all structures of the ipsilateral hippocampus, when compared to the unpaired control stimulation. An enhanced labeling occurred also in some structures of the contralateral hippocampus mainly receiving commissural inputs. The results suggest again, that the activation of one single hippocampal afferent, even if producing LTP, would not be sufficient to induce an increased glycosylation of neuronal proteins. The increase of glycoprotein formation seems to require the convergence of several inputs, which can be assumed to occur during learning. Therefore, LTP of a single synaptic population seems not to represent the complete long-lasting memory trace, but only one of its components, or a preceding transient storage mechanism.
Animals↗
Computer graphic study on models of the molybdenum cofactor of xanthine oxidase.
Within the scope of our molecular modeling studies on xanthine oxidase (XOD) inhibition by purine analogs we were interested to build up a three-dimensional model of the molybdenum active site. Spectroscopic data indicated that a Mo (VI)atom which is coordinated to sulfur, oxygen and/or nitrogen is clearly involved in substrate binding. In the present study, those data and X-ray crystallography data were used to reconstruct molybdenum-organic complexes from models proposed in the literature. The computer graphic-assisted modeling and evaluation of the model complexes show that the description of the molybdenum center needs further refinement.
Binding Sites↗
[Rehabilitation of chronic schizophrenic patients in long-term communities].
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Adolescent↗
[Special conditions for the cultivation of genetically engineered microorganisms].
Using recombinant strains recently the cultivation of microorganisms for biotechnological purposes has reached a qualitative new level. With respect to the optimization of such cultivation processes appropriate variations of genetical, physiological and biochemical parameters will be necessary. This review summarizes trends of construction of vectors and problems of correlations between hosts and vectors with regard to their application in discontinuous and continuous bioreactor-procedures.
Bacteria↗
Degradation of phenolic compounds by the yeast Candida tropicalis HP 15. II. Some properties of the first two enzymes of the degradation pathway.
The first two enzymes of the phenol degradation pathway were determined and characterized in crude extracts from Candida tropicalis HP 15. The phenol hydroxylase (EC 1.14.13.7) was a stable NADPH2- and FAD-dependent enzyme with a pH-optimum of 7.6 to 8.0 and a broad substrate specificity. Influence of ultrasound rapidly reduced the enzyme activity. The catechol 1,2-oxygenase (EC 1.13.1.1) had a broad pH-optimum between 7.5 and 9.6 and a limited substrate specificity. Two active protein bands indicating the presence of two isofunctional enzymes were detectable after electrophoretic separation of crude and partially purified extracts on polyacrylamide gels and specific staining for catechol 1,2-oxygenase activity.
Candida↗
Functional plasticity in two afferent systems of the granule cells in the rat dentate area: frequency-related changes, long-term potentiation and heterosynaptic depression.
Monosynaptic evoked field potentials (MEFP) were recorded in the dentate gyrus of male Wistar rats upon stimulation of either the perforant path or the commissural system. While the perforant path potential exhibited in acute experiments a clear reversal point of the field excitatory postsynaptic potential (EPSP) and population spike when protruding the registration electrode from the hippocampal fissura to the hilus of the dentate gyrus, the simultaneously registered commissural potential elicited by stimulation of the contralateral hilus showed no reversal of the negative monophasic wave but merely an amplitude maximum 40 microns above the reversal point of the perforant path potential. Frequency-related changes of the MEFPs during short tetanic stimulation with 15 Hz both in acute and chronic experiments, revealed differences in the properties of the input systems in that the commissural potential exhibited a clear frequency potentiation whereas the perforant path potential showed frequency depression. Pronounced long-term potentiation of the perforant path potential induced by 4 trains of tetanizing stimuli and lasting up to 72 h was accompanied by a long-term heterosynaptic depression of the commissural potential for up to 7 days after tetanization. Both the different frequency-related changes of the inputs and the extremely long duration of the heterosynaptic depression are discussed with respect to their proposed functions in the mechanisms of functional plasticity.
Animals↗