Biomedical subjects
Publications and source records attributed to H Matthies.
The convulsant effect of different doses of picrotoxin was investigated in pentylenetetrazol-kindled and saline-treated mice. The percentage of convulsions was greater in the kindled mice, compared to controls.
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.
Brain extract was obtained from whole brains of donor rats following four days of paradoxical sleep deprivation (PSD). Intraperitoneal injection of this brain extract in normal (i.e., not pretreated) recipient rats led to a significant increase of paradoxical sleep (PS) which was beginning at the third hour postinjection and still present on the day after treatment. Both PS episode number and PS episode duration were increased by the PSD extract, whereas slow-wave sleep was not influenced. Brain extract of nondeprived control rats, on the other hand, had no significant effects. In the present experiments, an extract volume obtained from two donor brains was transferred to one recipient. Compared to our earlier investigations (one donor brain/one recipient) this higher "dose" of PSD extract exerted a more pronounced and prolonged effect. These results support the idea that some PS-inducing factor(s) accumulating in the brain during PS deprivation may be involved in the regulation of paradoxical sleep.
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)
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.
Some D-amino acid-substituted derivatives of beta-casomorphin (CM) were found to exhibit a special affinity to central opiate receptors. Concerning their affinity to peripheral opiate receptors our knowledge is still limited. The results of our experiments indicate that CM derivatives interfere with peripheral opiate receptors and that there is a close connection with the affinity to different subtypes of this receptor.
Ionic currents of somata, acutely isolated from the terminal ganglion of the cockroach Periplaneta americana, were investigated by the intracellular perfusion technique. By the ratios of the amplitudes of the fast inward current to the stationary outward current all isolated neurons are classified into three groups. State 1 neurons are characterized by a large amplitude of the fast Na current. At its maximum (-20 mV) the stationary outward current is small. In state 3 neurons, an inward current could not be observed at any potential, but the stationary component of the outward current at -20 mV is already large. State 2 neurons represent an intermediate type. In state 3 neurons, no fast Na current could be observed even after elimination of the outward currents electrochemically (substitution of K ions by Tris ions) or pharmacologically (application of 2 mmol/l 4-aminopyridine and 50 mmol/l TEA-Cl). Instead of this, a Ca current was recorded although fluoride was used as the intracellular anion.
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.
Acute and chronic experiments were performed to study the effects of intraperitoneally administered dopamine receptor agonists and antagonists on the translocation of cytosolic and membrane-bound calmodulin in the striatum and hippocampus of the rat brain. Single doses of apomorphine and a low-dose amphetamine (1.25 mg/kg) resulted in a translocation of calmodulin, as measured by a decrease in membrane-bound and increase in cytosolic calmodulin in the striatum, whereas bromocryptine was ineffective. Amphetamine exerted a similar effect in the hippocampus and striatum. However, a high-dose amphetamine (5 mg/kg) had an opposite effect on translocation, in that there was an increase in membrane-bound calmodulin. Chronically applied amphetamine (5 mg/kg) and haloperidol (1 mg/kg), i.e. under conditions of dopamine receptor supersensitivity, tended to decrease cytosolic calmodulin in the striatum and hippocampus, and to increase membrane-bound calmodulin. The findings and, especially, the chronic effects of haloperidol and the high dose of amphetamine are interpreted in the light of the current concept which suggests that transmitters and intraneuronal signalling systems converge, thereby influencing the more complex processes of neuronal plasticity, rather than receptor sensitivity only.
The possible involvement of 2-amino-4-phosphonobutyrate (APB) recognition sites in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of D(-)- and L(+)-isomers of APB was tested on orthodromic EPSP and spike responses recorded extracellularly from CA1 pyramidal cells. If a moderate concentration (50 microM) of one or the other APB isomer was present during tetanization, posttetanic and early long-term potentiation developed nearly normally. However, from 2h onward LTP of both EPSP and spike potentiation was eliminated in an irreversible manner (8 h experiment). D-APB (L-isomer not tested) applied shortly after tetanization caused nearly the same delayed decline of LTP. No consistent effects of APB were seen in non-tetanized slices. Considering previous findings these data suggest that besides the obligatory NMDA receptor activation an APB-sensitive component expressed during and after tetanization is a necessary step for subsequent mechanisms enabling the late maintenance of LTP.
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.
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.
The possible involvement of N-methyl-D-aspartate (NMDA) receptors in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the specific NMDA receptor antagonists (-)-2-amino-7-phosphonoheptanoic acid (D-APH) and 2-amino-5-phosphonovaleric acid (DL-APV) as well as of the inactive isomer L-APH was tested on orthodromic population excitatory postsynaptic potential (EPSP) and population spike (PS) responses recorded extracellularly from CA1 pyramidal cells. If the active D-isomer of APH (10 microM) or DL-APV (50 microM), but not if L-APH was present during tetanization, both EPSP and spike potentiation were markedly reduced or even blocked for the whole recording period (8 h after tetanization). It is concluded that the NMDA receptor component expressed during tetanization is a necessary step not only for initiation but also for subsequent mechanisms enabling late phases of synaptic LTP. Some remaining potentiation of the population spike may be related to a second, NMDA-independent mechanism.
Rats from an albino stock were selected for high (HAS) and low (LAS) avoidance scores measured in a shuttle-box. Learning performance of male rats was compared in three different tests: the shuttle-box, the pole jumping-box, and the Y-chamber. It was shown that rats of the HAS line more rapidly acquired conditioned avoidance in the shuttle-box experiment and the pole-jumping experiment than LAS, whereas we could not detect any significant differences in brightness discrimination. In the open field test rats of the HAS line were more active in comparison to LAS's, measured in terms of higher ambulation scores. In conclusion, it is verified that the shuttle-box performance as well as pole-jumping performance is highly determined by the emotional status of the animals and, moreover, that avoidance learning is based on mechanisms other than brightness discrimination learning.
The effects of intraventricularly applied gangliosides (about 90 to 120 nmoles/10 microliters) and N-acetylneuraminic acid (800 nmoles/10 microliters) on acquisition and retention of a brightness discrimination task were studied in rats. Single injection of GT1b and N-acetylneuraminic acid improved the retention performance. GM1 showed an enhancing effect on both acquisition and retention, while GD1a and GD1b exerted no influence on the behavioral parameters tested. The findings presented show how memory may be improved by exogenous application of substances commonly occurring in the mammalian body.
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As determined by the HPLC technique, injection of 1.85 mmoles/kg D-galactosamine caused strong alterations in the plasma level of cytidime. Thus, 2 h and 4 h after application of the amino sugar only 54% and 61%, respectively, of the normal values were measured, while an increase to 135% of controls was observed 24 h later. In contrast, intraperitoneal application of D-galactosamine had no influence on the plasma level of uridine. The activity of the enzyme, uridine kinase, in the hippocampal area of the rat brain was increased 2 h and 4 h after D-galactosamine treatment. The results are discussed in the light of behavioural findings in which intraperitoneally applied D-galactosamine at this dosage improves the retention performance of an acquired behaviour in the rat.