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Biomedical subjects

W Pohle

Publications and source records attributed to W Pohle.

At least 19 recordsLinked to original sources
PubMed1992

Kindling and its consequences on learning in rats.

To study the learning performance of pentylenetetrazol- and amygdala-kindled Wistar rats we used the following learning tests: short-term memory was tested in the response-to-change model, brightness discrimination was tested in a Y-chamber, and two-way active avoidance learning was tested in a shuttle-box. Short-term memory was not impaired by both kindling procedures. Considering two-way active avoidance learning the performance of pentylenetetrazol (PTZ)-kindled rats was significantly diminished. This effect persists over a period of 4 weeks. However, amygdala (AMY)-kindled rats acquired this task like the controls. In brightness discrimination reaction (BDR) the learning performance of PTZ-kindled animals was not influenced. Although the acquisition of BDR was nearly identical, the 24-h retention was remarkably diminished in AMY-kindled rats. It was hypothesized that the different kindling procedures interfere in different ways and extent with neuronal circuits resulting in different functional impairments.

Amygdala↗
PubMed1992

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↗
PubMed1991

Enhanced development of morphine tolerance in rats treated with 2-deoxy-D-galactose.

Rats treated subcutaneously for 6 days with morphine developed a weak tolerance which was characterized by a decrease in the analgesic action of the opioid. Under those experimental conditions a simultaneous intracerebroventricular application of 2-deoxy-D-galactose enhanced development of morphine tolerance, while other deoxy-sugars like 2-deoxy-D-glucose and 6-deoxy-D-galactose were ineffective. In contrast, no influence of 2-deoxy-D-galactose on a more enhanced morphine tolerance after a 11-day pretreatment with morphine was found. The results are discussed in the light of a rather specific interference of 2-deoxy-D-galactose with neuronal glycoprotein processing and related cellular mechanism underlying adaptive processes involved in the development of morphine tolerance.

Analgesia↗
PubMed1991

Quantitative morphological analysis of hippocampal structures in DBA1 and DBA2 inbred mice strains with genetically determined different shuttle box behavior: the mossy fiber system with reference data to the C3H strain.

The present work deals with morphological aspects which are likely related to a genetically determined learning behavior in the shuttle box paradigm. Subregions of the hippocampal mossy fiber system in two closely related inbred mice strains, DBA1 as a bad active avoider and DBA2 as a good one, are compared. Additionally, data derived from C3H (bad active avoider) studies are analyzed. Beside of certain structural similarities in DBA1 and DBA2 such as the elongation of infrapyramidal mossy fibers along the CA3 neurons this study pays attention to the topography of hilus and basal CA3 mossy fiber innervation.

Animals↗
PubMed1990

Subsidiary hydrogen bonding of intercalated anthraquinonic anticancer drugs to DNA phosphate.

Several anthraquinone derivatives are active against different kinds of human cancer. The cancerostatic activity has been mainly attributed to their ability to bind strongly to DNA by intercalation. Here, infrared spectroscopy was used to detect further, more specific DNA interactions with the prominent anticancer drugs daunomycin, adriamycin, aclacinomycin A and mitoxantrone as well as with the cytotoxic violamycin BI. The most striking result was a significant decrease in wave number of the band arising from antisymmetric stretching vibration of the PO2- groups of DNA upon complexation with adriamycin, aclacinomycin A, violamycin BI and mitoxantrone. This became evident after separation of the contributions from conformational changes of DNA to the influence on the wave number of that band. The drug-induced shift was interpreted in terms of the formation of a hydrogen bond between the intercalated drug molecules and the PO2- moiety of DNA via the following terminal hydroxyl groups: C14-OH for adriamycin, C4-OH for both aclacinomycin A and violamycin BI and, more tentatively, the external side-chain OH of mitoxantrone. Theoretical considerations, consisting of semi-empirical CNDO/2 calculations as well as normal coordinate analyses performed with molecular model fragments, provided results confirming and rationalising the experimental findings. The capacities of the anthracyclines for restriction of the conformational flexibility of DNA differ, presumably due to variations in the spatial dimensions of the sugar moieties of the drugs. The compatibility of the present results with data obtained from current geometrical models, especially those for the DNA-daunomycin and DNA-adriamycin complexes, is discussed in detail.

Anthraquinones↗
PubMed1989

Complementarity of infrared linear dichroism and X-ray diffraction analysis as demonstrated by the study of a DNA-drug complex.

Infrared linear dichroism and X-ray diffraction analysis on oriented films and fibres, respectively, were used simultaneously to elucidate structural characteristics of a DNA-drug complex (the drug was the anticancer antibiotic violamycin BI, an anthracycline derivative). First, the parameters accessible by the two methods are briefly explained; then, attempts to inter-correlate the data from both lines of investigations are made, which demonstrate that they support and supplement each other favourably concerning several structural aspects. This holds, in particular, for results regarding the conformational flexibility of DNA in complexes and the relative amounts of intercalated and outside-bound drug molecules. Thus, the study represents an example for a successful combined application of two physical methods to one biochemical problem.

Aminoglycosides↗
PubMed1988

A biochemical and immunohistological study of calmodulin in rat brain structures.

Calmodulin content and immunoreactivity in rat brain structures, believed to be essential site involved in plasticity events, were determined by using biochemical and immunohistochemical methods, respectively. The levels of cytosolic and membrane-bound calmodulin paralleled the overall distribution pattern of calmodulin immunoreactivity. Very intense immunoreactivity was observed in neuronal structures of hippocampus, striatum and mesencephalon. White matter structures and, especially, myelinated nerve fibres did not reveal calmodulin immunoreactivity. Thus, the present findings are consistent with data reported in the literature that calmodulin, unlike to other calcium-binding proteins, is primarily associated with neuronal elements. The present findings support the usefulness of calmodulin studies in elucidating of cellular mechanisms underlying neuronal plasticity.

Animals↗
PubMed1988

Different effects of 2-deoxy-sugars on memory formation.

When rats were trained on a brightness discrimination task, intrahippocampal injections of 2-deoxy-galactose interfered with long-term memory formation while galactose and 2-deoxy-glucose were ineffective altogether. No differences were found in the morphology of hippocampal CA1 neurons investigated light-microscopically after application of the sugars. The amnestic action of 2-deoxy-galactose is discussed in the light of a rather specific interference with fucosylation of proteoglycans involved in mechanisms underlying the formation of a memory trace.

Animals↗
PubMed1988

Does avoidance learning only depend on mossy fiber distribution?

Rats and mice with a poor active avoidance behavior in the shuttle box exhibit a larger extent of the zone innervated by mossy fibers in the infrapyramidal area of the hippocampal sector CA3. The question arose whether only these differences in the amount of inputs from granular cells do correlate with poor avoidance learning, or whether cholinergic septal inputs are likewise related to behavioral performance. Inbred and non-inbred rats with low and high avoidance scores were used. Freezing sections were alternately used for TIMM-staining and for the histochemical visualization of the acetylcholinesterase activity. In comparison with "good avoidance learners" the rats with "poor active avoidance performance" exhibited a larger zone of mossy fibers and a lower activity of acetylcholinesterase in the investigated field. A significant inverse correlation between mossy fiber innervation and cholinergic septal inputs could be established. Our findings suggest that poor avoidance learning does not simply depend on mossy fiber distribution but seems to be dependent rather on the relation between mossy fiber innervation and cholinergic septal inputs.

Acetylcholinesterase↗
PubMed1987

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↗
PubMed1987

Colchicine-induced lesion of rat hippocampal granular cells prevents conditioned active avoidance with perforant path stimulation as conditioned stimulus, but not conditioned emotion.

Successful acquisition of active avoidance by rats with low frequency (15 cps) stimulation of the perforant path as a conditioning stimulus is correlated with a slowly developing long-term enhancement of perforant path-granular cell synapses. After selective destruction of granular cells of the stimulated side by unilateral microinjection of 1.6 micrograms/0.2 microliter colchicine into the dentate area, field potentials could no longer be evoked by test stimuli and animals subsequently failed to acquire the conditioned active avoidance with perforant path stimulation as a CS. However, colchicine-treated animals showed the same development of conditioned emotional responses as saline controls and they could also successfully be conditioned with light and tone as the CS. These results suggest that the granular cells are necessarily involved in the conditioning pathway for the active avoidance with perforant path stimulation as the CS. Other targets of the perforant path, e.g., ipsi- and contralateral CA1 pyramidal cells and contralateral granular cells, or antidromic activation of the entorhinal cortex seem an insufficient substitute for granular cells in the pathway for this conditioned active avoidance, but would probably participate in the conditioned emotional responses. The results additionally support our hypothesis, that post-conditioning LTP in granular cell synapses contribute to the acquisition and/or the storage of a memory trace.

Animals↗
PubMed1987

Transplantation of dentate granular cells after lesion of the dentate area by colchicine.

Colchicine selectively eliminated granular cells of the dentate area, and evoked potentials could no longer be recorded after perforant path stimulation. Colchicine treated rats were unable to learn a conditioned reaction via perforant path stimulation. The aim of this work was to investigate whether colchicine damaged granular cells could be replaced by grafting neonatal dentate area neurons. After injection of suspended granular cells no satisfactory development of grafted cells was seen, whereas granular cells of solid grafts did develop well, and a moderate reinnervation of the CA3-sector by mossy fibers sprouting out of the grafted cells was observed. In principle it is possible to replace colchicine damaged dentate granular cells by grafts in a few segments of the hippocampal formation. A total reconstitution of the damaged dentate area, including the mossy fiber system, will need a fundamental optimisation of the grafting technique used.

Animals↗
PubMed1986

Interaction of the C14-OH group of adriamycin with DNA phosphate as spectroscopically evidenced.

Monitoring the band of the antisymmetric stretching vibration of the backbone PO-2 group in DNA-anthracycline complexes demonstrates an extraordinary wavenumber shift for the adriamycin complex compared to that of daunomycin. The structures of both anthracyclines, however, are very closely related and differ only by a surplus hydroxyl group of adriamycin in the C14 position. The wavenumber shift observed for the DNA-adriamycin complex is unequivocally attributed to an additional linkage of the C14-OH of adriamycin to the phosphate group of DNA. Thus, several of the hypothetical structural models for the DNA-adriamycin complex for which a hydrogen bond between the C14 hydroxyl of the drug and DNA phosphate was postulated (S. Neidle, Cancer Treatment Rep. 61, 928 (1977); G. J. Quigley et. al., Proc. Natl. Acad. Sci. USA 77, 7204 (1980)) get the first clear-cut experimental evidence.

Animals↗
PubMed1986

The influence of experimental conditions on the morphological preservation of hippocampal slices in vitro.

The influence of different brain cutting techniques and various conditions of in vitro incubation on the morphological preservation of hippocampal slices was investigated comparatively. In order to obtain well-preserved slices great attention has to be paid to the immediate cooling of brain tissue to +4 degrees C and of all instruments as well. Under these conditions both the cutting technique and the incubation medium will be of subordinate importance. The incubation of 'interface slices' on a net in a slice chamber where the incubation medium flows constantly through the system and where the slices lay on the border to moistened oxygen is superior to the incubation of slices which are floating submerged in tubes--especially if the incubation time will last longer than 1.5 h. Different reliable incubation media did not show striking differences with regard to their effect on the preservation of hippocampal slices. New possibilities for incubation of slices for biochemical long-term investigations were tested and are discussed.

Animals↗
PubMed1985

Dopamine stimulated fucosylation of rat hippocampal proteins in vitro. A histoautoradiographic study.

The aim of the present investigation was to provide evidence for the topographic localization of dopamine (0.5 mM) stimulated L-[3H]fucose incorporation into rat hippocampal proteins in vitro. For this purpose, radiochemical estimations of fucosylation of hippocampal proteins were paralleled by histoautoradiography. The data of the radiochemical study showed a dopamine induced increase in L-[3H]fucose incorporation into hippocampal proteins by about + 120% compared to control values. Hippocampus slices from the same animals were processed for histoautoradiography. Under the influence of dopamine, L-[3H]fucose incorporation (estimated as silver grains either per cell or per square) was found to be significantly elevated in pericarya of granular cells as well as in the neuropil and in the glial cells of the stratum moleculare of the exposed blade of dentate area. This increase was most pronounced in the pericarya of granular cells, i.e. by about 200% over control level. With exception of fibres in the stratum lacunosum-moleculare of CA 1, the trends of increase in neurons, glial cells and fibre layers of other hippocampus subfields were not significant. The results may suggest that in rat hippocampus slices, dopamine induced increases in L-fucose incorporation are particularly localized in neurons of the exposed blade of dentate area.

Animals↗
PubMed1985

Autoradiographic assessment of [3H]proline uptake by neurons of epileptogenic mirror focus.

Epileptogenic mirror focus was produced in the left parietal area of the rat brain by cobalt implantation into the contralateral hemisphere. On the 14th day after cobalt implantation [3H]proline was injected into both experimental and control rats (without cobalt). The incorporation of [3H]proline in neurons of layers III and V of the parietal brain cortex and neurons of the nucleus lateralis thalami was investigated by the autoradiography technique. A statistically reliable increase in [3H]proline uptake was observed in neurons of layer III (31%) and in neurons of layer V (41%) of the epileptogenic mirror focus. The other neuronal types revealed no reliable changes. The morphological and functional aspects of the altered protein metabolism during epileptogenesis are discussed.

Animals↗
PubMed1984

Localization of entorhinal cortex neurons projecting to the dorsal hippocampal formation--a stereotaxic tool in three dimensions.

After topical injection of horseradish peroxidase into the dorsal hippocampal formation, the distribution of retrogradely labelled neurons of the entorhinal cortex was investigated. The distribution of these cells, which are projecting to the dorsal hippocampal formation, is demonstrated by drawings representing series of frontal, sagittal and horizontal sections and including stereotaxic coordinates. These drawings can be used as a morphological and stereotaxic tool in neurobiological research. Controversial opinions as to the dividing of the entorhinal cortex into subfields are discussed.

Afferent Pathways↗