Biomedical subjects

H Matthies

Publications and source records attributed to H Matthies.

At least 109 records · Page 6Linked to original sources

PubMed1985

The influence of enhanced K+-concentration on the uptake and acetylation of choline in hippocampus slices of rats.

The effect of K+-evoked acetylcholine (ACh) release on uptake and acetylation of choline (Ch) in hippocampus slices of rats was studied by use of two different temporal schedules of incubation with labeled precursor and K+-stimulation of tissue. When the incubation with labeled Ch was performed before K+-stimulation, a significant increase of ACh release up to about 400% could be observed. From hippocampus tissue Ch and ACh were extracted as free, labile bound and stable bound fractions. Immediately after the end of potassium stimulation only the ACh radioactivity of the labile bound fraction was decreased, whereas the Ch radioactivities were not changed. In a second series of experiments the K+-evoked ACh release was finished immediately, 10 or 25 min before incubation with labeled precursor. At this time the ACh radioactivity in the incubation medium was normalized. On the other hand, the Ch and ACh radioactivities in the hippocampus tissue increased and returned to control values by different time courses. 30 min after potassium stimulation the ACh radioactivities were still increased, whereas the Ch radioactivities were already normalized to control level. The calculation of the totals of released ACh radioactivity and Ch and ACh radioactivities of tissue suggests that the potassium evoked release leads to a higher uptake and acetylation irrespective of whether the stimulation was carried out before or after the incubation with labeled precursor.

Acetylcholine↗

PubMed1985

[Dopamine-stimulated glycosylation of rat hippocampal proteins in vitro: structure-response relationship].

Dopamine, but also other catecholamines (noradrenaline, adrenaline and isoprenaline), as well as L-dopa and alpha-methyl-dopa increase the incorporation of L-[1-3H]fucose into proteins of rat hippocampal slices. Among all substances that have been tested, dopamine exhibited the highest activity. Other non- or monohydroxylated phenylethylamine-derivatives (tyramine, octopamine, beta-phenylethylamine, metamphetamine) and pyrogallol had no effect on the fucosylation of hippocampal proteins. alpha-Methyl-dopa was less active than L-dopa. However, under the influence of alpha-methyl-dopa, an inhibitor of the dopadecarboxylase (aromatic L-amino acid decarboxylase, EC 4.1.1.28) the stimulatory effect of L-dopa on protein fucosylation was attenuated. From these results it is concluded that the dopamine-stimulated glycosylation of hippocampal proteins is triggered by (at least) two mechanisms, i.e. (1) via an activation of adenylate cyclase coupled dopamine receptor sites, and (2) via a mechanism which appears to be not related to an activation of transmitter-receptor sites but linked to the 3,4-dihydroxy-phenylethylamine-structure.

Animals↗

PubMed1984

Cholesterol oxidase susceptibility of the red cell membrane.

We have used the highly variable and conditional susceptibility of cholesterol oxidase to probe molecular rearrangements in the human red cell membrane. Cholesterol in the intact erythrocyte normally is not a substrate for this enzyme. Susceptibility was induced however, by these pretreatments: mild enrichment in membrane cholesterol, exposure to greater than or equal to 0.03% (3 mM) glutaraldehyde and warming in dilute salt solutions (mu approx. 0.001). Cholesterol reactivity in dilute salt solutions emerged only following a lag of 30 min or more. The lag time was shortened by raising the temperature, by reducing the salt concentration or by treating with glutaraldehyde. The induced sensitivity to the enzyme was inhibited by restoring physiologic ionic strength or by introducing 0.1 mol lysophosphatidylcholine per mol cholesterol into the membrane. (In striking contrast, lysophosphatidylethanolamine and lysophosphatidylserine did not inhibit oxidation). The various effectors of cholesterol oxidase sensitivity strongly influenced the impact of the others, suggesting that each shifted cholesterol toward or away from an enzyme-sensitive disposition. None of these effects was observed in pure cholesterol or red cell membrane lipids dissolved in detergent, which were uniformly highly reactive with the enzyme. We conclude that the observed variation in cholesterol oxidase sensitivity reflects changes in the organization of the bilayer, perhaps a lateral redistribution of lipids which creates cholesterol-rich phases or domains in which cholesterol is more or less accessible to the enzyme. If so, the time-dependent increase in cholesterol susceptibility during warming at low ionic strength might be a novel indicator of the kinetics of phase changes in the bilayer of the red cell.

3-Hydroxysteroid Dehydrogenases↗

PubMed1984

Dopamine-induced changes in protein phosphorylation and polyphosphoinositide metabolism in rat hippocampus.

Effects of dopamine (DA) on endogenous phosphorylation of hippocampal proteins and polyphosphoinositides were studied in subcellular fractions from a crude mitocondrial/synaptosomal preparation. DA induced a concentration-dependent decrease in the in vitro phosphorylation of the protein B-50 (-22.1% at 10(-5) M DA), whereas no changes were found in phosphoproteins in other subcellular fractions. Treatment of hippocampal slices with 5 X 10(-4) M DA resulted in a 45.8% increase in post hoc phosphorylation of B-50 in SPM and it affected post hoc phosphorylation of several proteins in a cytosolic fraction. In vitro phosphorylation of SPM with DA (5 X 10(-4) M) increased endogenous TPI phosphorylation (+51.6%), whereas treatment of slices with DA (5 X 10(-4) M) resulted in a 39.4% decrease in post hoc TPI phosphorylation. This decrease could be blocked by haloperidol. Significant changes induced by DA (5 X 10(-4) M) were also found in 32P-incorporation into PA (in vitro: -32.4% and post hoc: +39.3%), but were not found in DPI labeling. The data provide evidence for DA-induced changes in phosphorylation of proteins and polyphosphoinositides in rat hippocampal SPM.

Animals↗

PubMed1984

Effect of the memory-improving substance methylglucamine orotate on paradoxical sleep in rats.

The effects of methylglucamine orotate (MGO) were studied on polygraphic sleep recordings in rats for 8 h per day between 8 a.m. and 4 p.m. MGO (225 mg/kg) was injected intraperitoneally immediately prior to the onset of recording. In the acute experiment, the effect of MGO was compared to pre- and post-drug control days. In the chronic experiment, a sequence of 5 control days, 10 days of MGO treatment, and a further 8 control days was tested. Both acute and chronic administration of MGO resulted in increased paradoxical sleep (PS) latency and a small, but significant, decrease in PS during the first 4 h after injection. This effect seems to be specific to PS, as no effects of MGO on waking or total sleep were found. With chronic administration, no PS rebound occurred within the 8-h recording time during the 8-day post-treatment control period. How the RNA precursor can decrease PS and whether this effect may play a role in the memory-improving action of the substance is discussed in terms of an interrelationship between macromolecular synthesis, sleep, and memory, respectively.

Animals↗

PubMed1984

Perinatal linoleate deprivation impairs learning and memory in adult rats.

Rats receiving polyunsaturated fatty acid (PUFA) deficient diets during the perinatal period showed in adult age undisturbed acquisition of a footshock motivated brightness discrimination task, but a significant impairment of retention. The same effects on retention were obtained in rats receiving the PUFA deficient diet in adulthood, when the behavioral parameters were investigated at the end of the dietary treatment.

Animals↗

PubMed1984

Effect of apomorphine on retention of a brightness discrimination in dopamine supersensitive rats.

Apomorphine is known to improve the retention performance of a brightness discrimination task after post-training intrahippocampal application to rats. The present study shows that the retention performance of dopamine supersensitive rats was improved by a low dose of apomorphine which was still ineffective in control animals. Dopamine supersensitivity by itself had no effect on acquisition and retention parameters of brightness discrimination. The result further supports the assumption that dopamine receptors in rat hippocampus can modulate the formation of memory.

Animals↗

PubMed1984

Dopamine stimulated glycosylation of brain proteins in vitro is inhibited only partially by dopamine receptor antagonists.

Dopaminergic agonists which act on adenylate cyclase-linked dopamine receptor sites (D1-type) (dopamine, apomorphine and ADTN) induced a dose-dependent increase in the incorporation of L-fucose and D-mannose into glycoproteins of hippocampal, striatal and cortical slices of rat and mouse brain, whilst in rat liver slices dopamine failed to elicit such alterations in protein glycosylation. Testing in slices of rat hippocampus dopaminergic agonists with selective affinity to D2-receptors (bromocriptine, ergometrine) no changes in sugar incorporation into glycoproteins of rat hippocampus were observed. Dopamine stimulated L-fucose incorporation into rat hippocampal glycoproteins was inhibited to a different degree, but almost incompletely by dopamine receptor antagonists like haloperidol, D-butaclamol, promazine and alpha-flupenthixol, whilst chloropromazine and the selective D2-receptor antagonist sulpiride were without any effects. Also serotonin receptor antagonists (cinanserine) and beta-adrenergic receptor blockers (pindolol, alprenolol, practolol) failed to interfere with this dopamine action. But D,L-propranolol enhanced dopamine stimulated glycosylation of rat hippocampal proteins in an additive synergistic manner. This effect appeared to be not related to the antagonistic action of propranolol on beta-adrenergic receptor sites. From our results it is concluded that interactions with dopamine receptor sites (D1-type) is only one part of the mechanism triggering dopamine stimulated glycosylation of brain proteins in vitro.

Adrenergic beta-Antagonists↗

PubMed1984

Dopamine stimulated L-fucose incorporation into brain proteins is related to an increase in fucokinase activity.

Fucokinase (E.C. 2.7.1.52) activity was estimated in supernatant of homogenate from hippocampal slices. After an incubation of the slices in the presence of 0.5 mM dopamine a significant increase in the enzyme activity was observed. Under these conditions also an increase in the incorporation of [3H]fucose into hippocampal glycoproteins was observed. Thereby, the dopamine elicited changes in both fucokinase activity and fucose incorporation are similar in their time dependence. Moreover, dibutyryl-cyclic AMP led also to an increase in both fucokinase activity and sugar incorporation in hippocampal slices whereas cyclic AMP was without effect when added to the incubation mixture of the enzyme. The observed changes in fucokinase activity and its regulation by Ca2+ are discussed in terms of possible mechanisms realizing the dopamine stimulated fucosylation of rat hippocampal glycoproteins.

Animals↗

PubMed1984

Protective effect of uridine on D-galactosamine-induced deficiency in brain uridine phosphates.

In the rat, 2 h after intraventricular application of 10 mumoles D-galactosamine as well as 10 and 20 mumoles uridine, opposite effects on brain content of UDP-glucose and uracil nucleotides were observed. While D-galactosamine caused a strong decrease in content of uridine phosphates, the brain content of the latter substances was markedly increased after uridine application. Furthermore, 20 mumoles uridine applied 10 min prior to D-galactosamine administration prevented the D-galactosamine-induced drop in brain uridine phosphates. The results are discussed in the light of behavioural findings in which D-galactosamine-induced impairment of retention performance of an acquired behaviour could be abolished by uridine pretreatment.

Animals↗

PubMed1984

Changes in the incorporation of [3H]leucine into proteins of rat hippocampus subregions during the acquisition of a brightness discrimination are lateralized.

The incorporation of intraventricularly injected L-[4,5-3H]leucine into proteins of rat hippocampus subregions ("CA 1", "CA 3" and "Ca 4/area dentata") was studied during the acquisition of a footshock-motivated brightness discrimination. In passive controls, protein synthesis rates in CA 3 was significantly increased over those of CA 1 and CA 4/area dentata. Moreover, in left CA 3 L-leucine incorporation rates were significantly elevated when compared to those of the controlateral side. These differences between hippocampus subregions and left and right CA 3 were found to be not dependent on the technique of L-leucine application, but left-right differences did not exist under in vitro conditions. During training, protein synthesis rate in right CA 3 was increased by about + 30% (p less than 0.05) over that of active or passive controls. The trend in CA 1 was not significant. Protein labelling in left hippocampal subregions and, in addition, right CA 4/area dentata exhibited no differences between trained and non-trained animals. Pretreatment of rats with uridine-5'-phosphate improving long-term memory formation resulted in an augmentation of L-leucine incorporation into proteins of CA 1 and CA 3 of trained animals when compared to controls, whilst in other hippocampal subregions no differences in incorporation rates were found between trained and nontrained rats. The present data provided evidence for a hemispheric asymmetry of training-induced changes in protein synthesis in CA 1 and CA 3 of rat hippocampus.

Animals↗

PubMed1983

Memory retention in old rats: improvement by orotic acid.

The effect of methylglucamine orotate (MGO) on learning and memory was investigated in 24-month-old rats using brightness discrimination in a Y-chamber and active avoidance in a shuttle box. In both learning procedures, an improvement of memory retention following 5-day MGO treatment (225 mg/kg per day) was observed. The retention of untreated old animals was significantly lower compared to 8-week-old rats. MGO treatment resulted in a significant improvement of retention in old rats, which nearly compensated for their memory deficit.

Aging↗

PubMed1983

Changes in activities of fucokinase and fucosyltransferase in rat hippocampus after acquisition of a brightness discrimination reaction.

Activities of enzymes involved in utilization of the glycoprotein precursor L-fucose (fucokinase and fucosyltransferase) were studied in rat hippocampal tissue after acquisition of a brightness discrimination reaction. Fucokinase activity was increased immediately after training, while fucosyltransferase revealed decreased values. However, 7 hr after training fucokinase activity showed normal values, while fucosyltransferase activity rose in trained animals over active and passive controls. The results are discussed in the light of a regulatory role that fucokinase and fucosyltransferase may play in fucose utilization under altered functional conditions.

Animals↗

PubMed1983

PAGE-autoradiography of fucose incorporation into rat hippocampal glycoproteins after acquisition of a brightness discrimination.

Male rats aged 8 weeks received intraventricular injections of 100 microCi (3.7 MBq) L-[1-3H] fucose each, 7 h after acquisition of a brightness discrimination task. Two, 8 and 24 h as well as 16, 29 and 60 days after injection of labelled fucose hippocampal tissue was prepared to obtain Tris-soluble, Triton-soluble and Triton-resistant fractions. Two and 8 h after application of [3H]fucose, the trained animals revealed an increased incorporation of fucose mainly into the Triton-soluble glycoproteins. However, it is considered that also material from the Tris-soluble fraction may be used as an additional precursor for Triton-soluble glycoproteins. Quantitative analysis of autoradiographic densitograms obtained after SDS-polyacrylamide gel electrophoresis showed the occurrence of a training-related increase in fucose incorporation predominantly into the slow-moving Triton-soluble glycoproteins. The latter exhibited a higher turnover rate than the faster-moving glycoproteins. For the longer incorporation times (days) after injection of labelled fucose, no differences were observed between trained animals and corresponding active and passive controls.

Animals↗

PubMed1983

The effect of dopamine on L-fucose incorporation into hippocampal and striatal slices of dopamine-supersensitive rats.

The incorporation of L-[1-3H]fucose into total proteins was measured in hippocampal and striatal slices of dopamine-supersensitive and control rats. Compared with controls, striatal slices of supersensitive animals exhibited an augmented stimulation of L-fucose incorporation by 5 X 10(-5) M dopamine. This result supports former data about a dopamine-receptor mediated regulation of protein glycosylation in the nervous tissue.

Animals↗

PubMed1982

Differences in Y-maze retention of rats: selection according to open field activity.

Adult male Wistar rats of a heterogeneous outbred population were selected according to their open field ambulation and classified into two groups: animals showing the most activity during the first 2 min (A, fast habituation), or after the first 2 min (B, delayed habituation) of a 10 min observation period. One week later these rats were tested for foot-shock motivated brightness discrimination learning and retention in a Y-maze. It was found that group A rats exhibited higher %-savings than group B rats, whereas their learning performance was not different. Thus, our results show that rats differing in their Y-maze retention ability can be selected on the basis of certain open field measures.

Animals↗

PubMed1982

Monosynaptic activation of the hippocampus as a conditioned stimulus: behavioral effects.

The aim of the present study with rats was to show that electrical stimulation of a monosynaptic pathway, whose high plastic potency is well-known, can serve as a conditioned stimulus (CS) in a learning paradigm. Using chronic rats, stimulation of the perforant pathway, which activates the entorhinal cortex input to the dentate gyrus of the hippocampus, was used as the CS in a footshock motivated two-way avoidance task (shuttle box). Among the different stimulation parameters tested, only trains of at least 15 Hz were shown to be effective as a CS, whereas the application of single impulses with a frequency of 1,7 Hz did not result in the establishment of conditioned behavior. Using the 15 Hz-paradigm, in "good learners," the development of reliable conditioned responses started at the end of the first training session (40 trials) and become fairly stable during a further training session, given on the following day. The application of stimulation trains with 100 Hz as a CS led to the development of a high rate of conditioned responses, however, there was also a high level of intertrial reactions. Considering the critical importance of the frequency parameters of the perforant pathway stimulation for the development of conditioned behavior the possible involvement of hippocampal long-term potentiation in behavioral plasticity is discussed. Additionally, it is concluded that this new learning paradigm offers the advantage of concurrent analysis of plastic processes both at the behavioral level and at the level of the synaptic population.

Animals↗

PubMed1982

Mechanisms of dopamine induced changes in hippocampal glycoprotein metabolism.

In rat hippocampal slices incubated in the presence of dopamine, a relatively strong correlation was observed between changes in the incorporation of 3H-fucose into total proteins and the formation of GDP-3H-fucose. However, in hippocampal homogenate the incorporation of 14C-fucose from GDP-14C-fucose was not stimulated by dopamine. In contrast, the incorporation of 3H-fucose was stimulated by dopamine to a similar extent observed in hippocampal slices. Furthermore, in hippocampal slices dopamine did not increase the activity of fucosyltransferase. These results, together with our previous findings, suggest that the increased incorporation of fucose induced by dopamine in the hippocampal slices may be due to a receptor-mediated cAMP-dependent regulation, which controls the rate of fucosylation of acceptor-glycoproteins either at the level of fucose phosphorylation or of formation of GDP-fucose rather than the activity of fucosyltransferase.

Animals↗