Biomedical subjects
Publications and source records attributed to H Matthies.
Apomorphine intrahippocampally injected at a dose of 5 microgram led to a significant increase in incorporation of (3H)-fucose into total proteins of this brain area, whereas 40 microgram led to a significant decrease in comparison to controls, providing further evidence for the existence of dopaminoceptive structures in the hippocampus of rats and their significance for glycoprotein metabolism.
The effect of serotonin (5-HT) on consolidation of a brightness discrimination reaction was investigated in rats. Five microgram 5-HT, injected intrahippocampally immediately after training, impaired retention of the brightness discrimination tested 24 hr later. In biochemical experiments, leucine incorporation into hippocampal proteins in vivo was 32% inhibited by 5 microgram 5-HT. Leucine incorporation into proteins of hippocampal slices in vitro was decreased by 5 x 10(-5)M 5-HT. The results seem to support Essman's assumption that inhibition of brain protein synthesis by 5-HT may be responsible for the memory impairment. But also some other possibilities for a mechanism of 5-HT amnesia must be discussed.
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Ten mumoles of intraventricularly injected D-galactosamine (GalN) inhibited the incorporation of [(3)H]-guanosine and [(3)H]-leucine into RNA and protein of the rat hippocampus, respectively. The inhibition of guanosine incorporation of appr. 80% occurred during the first 30 min after GalN treatment and lasted at least 4 h. The incorporation of leucine was inhibited by appr. 30% only; this effect occurred not earlier than 90 min after GalN injection. The results demonstrate a similar effect of GalN on brain macromolecular syntheses as already observed in the liver suggesting the same mechanism of action, namely trapping of uridine phosphates. The results are discussed with regard to the amnesic effect of GalN observed on the retention of a brightness discrimination in rats.
In 40 rats immobilized with gallamine evoked field potentials were elicited in the dorsal hippocampus by stimulation of the septal nuclei. Latency of the septohippocampal evoked potential (SHEP) elicited by stimulation of the medial septal nuclei, the variations of latencies and amplitudes with increasing stimulus intensities as well as the occurrence of frequency potentiation and post-tetanic potentiation allow the conclusion that the SHEP registered in the stratum granulare of dentate gyrus is mainly monosynaptically elicited. Nevertheless some data discussed in the paper point to the existence of a more complicated and not exclusively monosynaptic activation of granular cells caused by septal stimulation.
In the present paper the behaviour of the enzymes monoaminoxidase, GABA-transaminase, acetylcholinesterase, nonspecific cholinesterase, A-, B-, C-esterase and acid phosphatase was investigated by histochemical and biochemical methods for 1 min, 1, 4 and 24 h after a "brightness-discrimination" of male wistar rats in a Y-chamber. Learning induced significant changes of activity of the B-esterase in the hippocampus region 4 h (increase of 30%) and 24 h (decrease of 25%) and of the acetylcholinesterase in the cingular cortex 4 h after training (increase of 38%) are to be observed and regarded and discussed as hints for a changed protein synthesis (B-esterase) or altered synaptic activity (acetylcholinesterase). On the strength of these results and various findings in the literature it may be reputed as sure, that the protein synthesis of the cells of hippocampus in evident. Certain proteins show increased rates of synthesis by the influence of a learning experiment. These proteins are at least partially enzymes, serving as extension of the protein synthesis apparatus of the neurons and may be regarded as part mechanism of the intracellular regulation of the synaptic connectivity.
1. In 40 three months old Wistar rats (16 trained animals, 14 active controls, 10 passive controls) the influence of learning (brightness discrimination) on the number of electronmicroscopically detectable synapses per area neuropil was studied in the stratum radiatum (CA 1) of the hippocampus. 2. 70 minutes after completion of training, the mean number of synapses has significantly increased as compared to active controls (trained animals 14.26 +/- 2.95 synapses/25 micrometer2; active controls 10.23 +/- 2.80 synapses/25 micrometer2; p less than 0.001). 3. 24 hours after training this increase in trained animals still persisted (trained animals 14.15 +/- 2.60, active controls 11.39 +/- 2.87 synapses/25 micrometer2; p less tha 0.001). 4. 14 days after training, the number of synapses has decreased considerably, but was nevertheless significantly higher than in the active controls (trained animals 12.49 +/- 2.76, active controls 11.45 +/- 3.10; p less than 0.001). 5. The results are discussed with regard to their significance to the different stages of memory formation in the CNS.
In the rat, intraventricularly applied D-galactosamine (GalN) (10 or 20 mumoles) inhibited [(3)H]-fucose incoporation into hippocampal and subcortical glycoproteins by appr. 50% of the controls. The inhibitory effect occurred within 40 min after GalN administration and did not reach normal values even 16 h upon GalN injection. During the first hours upon GalN administration the inhibition of fucose incorporation involved predominanatly water-soluble and Triton-soluble glycoproteins, whereas the Triton-resistant fraction showed a delayed suppression. The results suggest that GalN suppresses the formaton of membrane glycoproteins (because only 15% of fucose radioactivity remained in water-soluble fraction) which are believed to play an essential role in formation of long-term memory. Under these aspects, the amnesic effect of GalN on the retention of a brightness discrimination and the abolishment by uridine treatment, as observed in our laboratory, may be interpreted as a further support to the particular role of glycoproteins in the consolidation of a memory trace.
The effects of methylglucamine orotate (MGO) on the retention of a brightness discrimination in rats was investigated after different intervals between treatment and acquisition, 225 mg MGO/kg were injected intraperitoneally each day over a period of 10 days. Control animals received a NaCl-solution. After drug-free intervals of 5 days or 12 days respectively, MGO-treated rats showed significantly better retention of the learned reaction than controls, whereas their training performance was not influenced. Possible interpretations of the long-lasting persistence of the orotate effect are discussed.
Am method is presented which enables the incorporation of solubilized brain membrane proteins into bilayer lipid membranes (BLM) from brain lipids. The digitonin solubilized proteins are first incorporated into liposomes which undergo fusion with the BLM in a second step. The incorporation results in a large increase in membrane conductivity which maintains at a stable level for hours. Identical electrical phenomena were observed after incorporation of the membrane fragments which were used as starting material of protein extraction. The method can be used to reconstitute membrane proteins to the their natural lipid environment in a planar BLM. Our results argue against the essential role of Ca2+ and osmotic gradients during fusion of bilayer structures.
A reliable method for visualization of mannose-containing glycoproteins in electrophoretically (SDS-PAGE) separated Tris-soluble, Triton-soluble and Triton-resistant fractions obtained from rat hippocampus, brain region supposed to play an essential role in learning and memory processes, was elaborated. The method is based on the Concanavalin A-horseradish peroxidase reaction applied successfully for the purpose of light and electron microscopic visualization of cellular carbohydrate components.
During the postnatal period, male Wistar rats were treated with orotate, either from the 6th to 15th, 16th to 25th, or 26th to 35th day of life. Learning and memory were tested in adulthood. Rats that received orotate from the 6th to 15th day showed a better retention of a learned brightness discrimination (Y-maze) than controls. An active avoidance (pole jumping) was learned more quickly by the rats orotate-treated from the 6th to 15th day than by controls. The spontaneous locomotor activity of previously orotate-treated rats was the same as in controls. Body weight measurements revealed no differences between orotate rats and control rats. The results suggest that memory retention in adulthood can be improved by postnatal orotate treatment.
The incorporation of (14C)-leucine into the total proteins of the hippocampus is inhibited by high concentrations of cholinergic agonists, with nicotinic substances (such as 1,1-dimethyl-4-phenyl-piperazine) being more effective than muscarinic compounds (such as arecoline and pilocarpine). Under these conditions the incorporation of (3H)-fucose is not influenced.
In hippocampus slices both dopamine and apomorphine lead to an increased incorporation of (3H)-fucose into total proteins, whereas the incorporation of (14C)-leucine was unchanged or decreased, respectively. Noradrenaline did not alter the incorporation of both precursors, whereas haloperidol partially reduced the dopamine induced increase in incorporation of fucose. Thus, an induction process of the observed macromolecular changes involving dopaminoceptive structures of hippocampus can be assumed.
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Using a brigthness discrimination model in rats, the labeling of discrete hippocampus formation structures was studied after intraventricular application of [3H]-fucose. This substance was injected 5 min before training as well as 5 min, 3, 7 and 23 h after training, the pulse period lasting 120 min in all cases. A significantly training-related enhanced labeling of CA1, CA3 and CA4 cell bodies and fibres revealed that a biphasic time course occurring when radioactive fucose was applied 5 min before training and 7 h after training, whereas the increased labeling of area dentata structures was evidenced only after application of radioactive fucose 5 min before and after training. In all structures under investigation the training-related increase in labeling was more pronounced in the fibre layers than in the pyramidal and granular cell bodies.
Rat brain histones were acetylated in vivo by intraventricular injection of [14C]-acetate. More than 90% of the label is the result of a true acetylation. Enzymatic proteolysis of the labelled histone fraction and subsequent chromatographic investigation of the digestion products showed about 60% of the recovered radioactive material to be epsilon-acetyl lysine, whereas 22% of the radioactivity was found in an unidentified spot.