[Cajal's neuronal theories today].
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Biomedical subjects
E Winkelmann
Publications and source records attributed to E Winkelmann.
Morphology of neurons in the rat basal forebrain nuclei: comparison between NADPH-diaphorase histochemistry and immunohistochemistry of glutamic acid decarboxylase, choline acetyltransferase, somatostatin and parvalbumin.
Transversal sections through the basal forebrain of 11 adult male rats were immunostained for glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT), somatostatin (SOM) and parvalbumin (PARV). Immunohistochemistry of ChAT, PARV, and SOM was combined with histochemistry of NADPH-diaphorase (NADPH-d) to obtain information on the colocalization of various neuroactive substances and this enzyme and to facilitate the recognition of morphological details of double-stained neurons. The distribution patterns of GAD- and PARV-immunoreactive cells were only in part congruent in basal forebrain nuclei in the rat. In the medial septal nucleus (MS) and the vertical limb of the diagonal band (vDB) PARV-immunopositive neurons were homogeneously scattered inside the nucleus, whereas the GAD-immunoreactive cells were much more numerous in the lateral part of this nuclear complex. In the horizontal limb of the diagonal band (hDB) and the nucleus preopticus magnocellularis (NPM), where GAD-immunoreactive cells occurred in high number, only very few cells contained PARV-immunoreaction product. In the substantia innominata-nucleus basalis Meynert complex (SI-NB) and in the ventral pallidum (VP) the neuropil was heavily stained with the GAD-immunoreaction product. The number of GAD-positive cells appeared low in the SI-NB, but much higher in the VP. In this nucleus GAD- and PARV-immunoreactive cells seem to be identical. PARV-positive neurons are very sparse in the SI-NB. Double-staining of PARV-immunoreactivity and NADPH-d was not registered. These nuclei were the only ones in which some cells with SOM-like immunoreactivity were observed. Among ChAT-positive neurons those double-stained with NADPH-d occurred in moderate number, but with obvious regional differences. In MS-vDB and the marginal zone of hDB the two neuron groups were intermingled, but only in the innermost part of the hDB ChAT-single-immunostained cells form aggregates, which were also typical of the zone in the SI-NB that surrounds and infiltrates the globus pallidus (GP). Double-labelled cells were more frequent in the lateral aspect of the NPM and SI-NB. Cells single-stained for NADPH-d were frequent in the MS-vDB along the border toward the lateral septal nuclei, but low in number in the NPM, VP and SI-NB. The functional aspects of the occurrence of GAD-immunoreactive cell aggregates in the lateral preoptic area (LP) and the lateral hypothalamic area (LH) were discussed with special regards to extrinsic GABAergic input in the dorsal SI-NB.(ABSTRACT TRUNCATED AT 400 WORDS)
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[Neurons in the visual cortex of Microtus brandti].
Neurons were described in the visual Cortex of Microtus brandti, a Mongolian harmful rodent living in day-activity. We find following types of neurons in our Golgi-material: 1. spiny neurons: pyramidal and stellate neurons. 2. smooth or sparsely spined neurons: smooth, large neurons, sparsely spined small neurons with descending axons, sparsely spined neurons with ascending axons. Double-bouquet-, chandelier and neuroglioforme cells are not impregnated. There are no bipolare neurons (Martinotti cells) among the neurons with ascending axons. The small, sparsely spined neurons are not only in lamina IV - like in other species - but they can also be found in laminae II to IV. Their distribution of spines on the distal parts of dendrites seems to be characteristical for rodents. The lamination of the visual cortex of Microtus brandti is the same like in the rat. All cells are of large size in relation to the body mass of the animal.
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[Neuronal structure abnormality in the orbito-frontal cortex of schizophrenics].
Changes were described in the neuronal structure of neurones, impregnated after the method of Golgi-Bubenaite in schizophrenic patients. Investigations were done in area 11 (Brodmann 1909) of patients with paranoid-hallucinatory schizophrenia. Control cases were patients without any clinical or morphological brain diseases and patients with catatonic schizophrenia. 1.1 We investigated numerous typical triangle cells in lamina VI of patients with paranoid-hallucinatory schizophrenia. Only few were seen in the controls. 1.2 In the paranoid-hallucinatory schizophrenia brains there are lamina VI pyramidal cells with ramified apical dendrites reaching lamina II. 2. In lamina V there are many pyramidal cells with two to five apical dendrites, such cells were never seen in controls, these pyramids have only one main apical dendrite. 3. A small group of L III pyramids have atypical long spines. A lot of these spines have splitted spine heads. The spine number is significantly increased. 4. There is an atypical simplified angioarchitecture in paranoid hallucinatory schizophrenia-patients and no normal arborization of the brain vessels in three planes, like in controls. We think that the abnormal findings in paranoid-hallucinatory schizophrenia are not the consequence of specific therapeutics. We interpret our findings as possible variabilities of a normal brain structure.
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[Expansion and thickness of the visual cortex of microphthalmic mice and healthy Wistar animals].
In connection with our studies about the development and the structure of the visual system of the brain of normal and genetically microphthalmic mice in this paper we have investigated the extend of the visual cortex and the thickness of the primary visual cortex (area Oc1). The most important results are: The size of the surface of the neocortex and of the areas Oc1 and Oc2m shows no significant differences between the normal and the microphthalmic mice. The whole thickness of area Oc1 is at day 20 in the microphthalmic mice significantly greater than in normal animals. In the microphthalmic mice lamina I, III and V are thicker than in normal mice. Lamina IV is in microphthalmic mice significantly thinner than in normal animals. The interpretation of these results is difficult because at PD 20 the cortex and his laminae are not full developed. But there are in the microphthalmic mice not such clear changes (reduction) on the cortical level as in the subcortical structures of the visual system. The reduction of the thickness of lamina IV maybe caused by a reduced projection from the lateral geniculate nucleus.
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Antiviral activity and pharmacokinetics of HOE 602, an acyclic nucleoside, in animal models.
The acyclic nucleoside derivative HOE 602 (2-amino-9-[1,3-bis(isopropoxy)-2-propoxymethyl]purine) was evaluated for its antiviral activity in cell culture and for its therapeutic efficacy in mice infected with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) or with murine cytomegalovirus (MCMV). HOE 602 was inactive in vitro against a variety of DNA- and RNA-viruses. However it prevented symptoms and mortality in mice systemically infected with HSV-1, HSV-2 or MCMV when administered intraperitoneally or orally at a dosage of 100 mumol/kg twice per day. Pharmacokinetic studies in mice and macaques revealed that HOE 602 was converted via three metabolic steps to ganciclovir, which seemed to be the antivirally active compound. The bioavailability of ganciclovir after oral administration of HOE 602 or ganciclovir was similar in mice, while in rhesus monkeys much higher serum levels of ganciclovir were reached with HOE 602. After intraperitoneal or intravenous administration higher drug levels were obtained with ganciclovir. The excellent therapeutic efficacy in animal models, the high enteral absorption in monkeys, and the favourable physical properties will hopefully lead to an orally active drug against cytomegalovirus and severe herpes infections in man.
Acyclovir↗
[Characterization of the neurons of the basal forebrain complex in the rat: A Nissl- and Golgi impregnation study].
Nissl stained neurons were classified in some nuclei of the basal forebrain complex of the rat (Nc. septi medialis, MS; vertical limb of the nucleus of the diagonal band, vDB; horizontal limb of the nucleus of the diagonal band, hDB; Nc. preopticus magnocellularis, NPM; Substantia innominata, SI; Nc. basalis Meynert, NB). Several types of neurons are coexistent in each of these nuclei. They differ in soma size and shape, but also in their cytoplasmic and nuclear texture. We found three classes of neurons as well in the MS-vDB, as in the hDB and NPM, but five classes in the SI-NB complex. On the basis of these findings some conclusions were drawn regarding the cytoarchitecture of this region, as the demarcation of vDB and hDB and of hDB and NPM. The borderline between vDB and hDB was found to be undefinable in Nissl stained preparations, whereas the NPM is characterized by its high content of giant neurons in cotontrast the adjacent hDB. Additionally, we tried to identify the Nissl stained neurons on the basis of soma features with Golgi impregnated neurons. The daimpregnations of Golgi impregnated neurons enabled us to compare the width of the cytoplasm and the nuclear position of neurons stained after these methods. From the thirteen classes of neurons described in Golgi investigations, 8 were identified in Nissl stained sections through this region of the rat's forebrain.
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[Gabaergic NADPH-diaphorase-positive Martinotti cells in the visual cortex in rats].
NADPH-diaphorase positive cells were described in the visual cortex of the rat in layers II-VI and in the white matter. Their somata were large or medium-sized, oval or elongated, and their cytoplasm was accumulated at the poles. Some proximal thickened coarse dendrites formed a bitufted dendritic field. These features showed a cell type impregnated with the Golgi-Kopsch-method and a Golgi-deimpregnation-method described as Martinotti cell (sparsely spined polarized neurons with ascending axons). The immunocytochemical evidence of GABA in NADPH-diaphorase positive neurons (double labeling) showed the GABA ergic nature of these cells, but an attempt for a double labelling of NADPH-diaphorase and Parvalbumin was negative.
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Ultrastructure of neurons and their synaptic contacts in the medial septal nucleus of the rat.
The medial septal nucleus of non-experimentally treated albino rats was investigated electron microscopically. According to former light microscopical findings most of the dendrites in this region are spineless but conspicuously varicose. Besides a striking diminution of the packing density of neurotubules inside the varicosities--compared with the narrow portions of varicose dendrites--some organelles like multivesicular bodies, lamellated bodies and cisterns of the smooth endoplasmic reticulum were found to be characteristic of them. Large neuronal somata rich in RER with a broad rim of cytoplasm around the nucleus and numerous lipofuscin-like granules occur. But there are numerous small cells exhibiting a narrow rim of cytoplasm and pourly developed RER, too. At least six classes of synaptic junctions can be distinguished, three of the asymmetric and three of the symmetric type. Most of axo-somatic contacts are of the symmetric type, at the dendrites asymmetric contacts dominate. Presynaptic profiles with large dense-core vesicles form symmetrical contacts with varicose and non-varicose dendritic profiles.
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A Golgi deimpregnation study of neurons in the rhesus monkey visual cortex (areas 17 and 18).
The morphological features of 298 neurons impregnated according to Golgi-Kopsch in areas 17 and 18 of Macaca mulatta were analyzed, and the same neurons were deimpregnated to visualize structural details of the somata in different types of neurons. The following cell types were investigated: Pyramidal and pyramid-like cells, spiny stellate cells, double bouquet cells, bipolar cells, chandelier cells, neurogliaform cells, basket and related cells. This procedure allows the evaluation of the nuclear-cytoplasmic proportion and the position of the nucleus besides shape and size of the cell body. Pyramidal and pyramid-like cells (N = 43), spiny stellate cells (N = 26), basket and related cells (N = 126) are variable in these features. A positive correlation between soma size and width of the cytoplasm is found in pyramidal, pyramid-like cells and spiny stellate cells. With the exception of some large somata in both these types of neurons the nucleus is found in a central position. Double bouquet cells (N = 6), bipolar cells (N = 13) and chandelier cells (N = 11) exhibit small cytoplasmic rims and centrally located nuclei. The small somata of neurogliaform cells (N = 37), however, and the small to very large somata of basket and related cells show broad cytoplasmic portions surrounding the eccentrically located nuclei. These findings allow the identification of different neuronal types in Nissl-stained sections on the basis of these soma features. This is a prerequisite for further detailed quantitative studies on the laminar distribution of different neuronal types in the visual cortex of the monkey.
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[The classification of neurons in the corpus geniculatum laterale pars ventralis of the albino rat: a Golgi-Kopsch study].
Neurons in the ventral lateral geniculate nucleus of 120 rats of a wistar strain were investigated with the Golgi Kopsch technique. Various features, such as size of neurons, their dendritic fine structure and their localization inside the nucleus were used to find new aspects for the classification of vLGN neurons except geniculo tectal relay neurons (GTR neurons). The results of our detailed investigation are in accordance with the classification given by Brauer et al. (1984). The dendrites show different morphological surface specializations, as there are smooth and varicose dendrites besides the spiny ones. Medium-sized neurons are most variable in their dendritic structure. It can be assumed that they represent a heterogenous group. The density of spines in the neurons investigated is much lower than in GTR neurons.
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Shape and size of synaptic vesicles in different types of presynaptic profiles in the medial septal nucleus of the rat.
Long and short axis diameters of synaptic vesicles were obtained from 6 classes of presynaptic boutons found in the medial septal nucleus (MS) of the rat. The variability of vesicle size and shape was documented in diagrams and discussed with regard to their suitability as criteria of classification and their functional significance. The variability in shape, but not in size, of vesicles in synapses of Gray's type I is lower than of those in Gray's type II synapses.
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[Comparison of relay neurons in the lateral geniculate body of normal, bilaterally enucleated and congenitally blind strain 944 mice during ontogenesis].
Mice with normal visus, bilaterally enucleated and congenitally blind mice of the strain 944 were used to determine following parameters in the CGLd on day 5, 10, 15 and 20 post natum (Golgi impregnation): size of neurons (perikarya, size of dendritic domains DF), structure of dendrites (number of dendrites FDE, branching points VZP, distribution of dendritic density in relation to the perikaryon Is, number of primary dendrites). After Nissl staining the following parameters were investigated: volume of the CGLd, packing density and total number of cells in the CGLd. The differences between the three investigated groups of animals increase in changing amounts during the ontogenesis. The caudal part of the CGLd is altered mostly by the lacking optic events. Suppression of visual events during the normal ontogenesis caused by genetic defect or enucleation attacks the same structures of the neuron.
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[Volumetric and golgi studies of the corpus geniculatum laterale pars dorsalis of Alticola stoliczkanus barakshin and Alticola argentatus semicanus].
The dorsal lateral geniculate bodies (dLGB) in Alticola stoliczkanus barakshin, the Gobi-Altai-Mountain vole, and in Alticola argentatus semicanus, the silver grey mountain vole, and investigated using the nissl- and the golgi method. The geniculo-cortico-relay neurons (GCR neurons) of both species have 5 primary dendrites (D1), a dendritic field of about 100 micron, about 17 free dendritic distal parts (FDE), 10 branching points (VZP) and a average of the perikaryon of 10 micron. All tufted neurons are small and topographically distinctly localised. The dLGB's volume of Alticola stoczkanus, barakshin is 0.16 mm3, the dLGB's volume of Alticola argentatus semicanus is 0.23 mm3.
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Topographic differences in retinal axons in the dorsal lateral geniculate nucleus of the rat: a quantitative reexamination using anterograde transport of horseradish peroxidase.
Retinal endings in the dorsal lateral geniculate nucleus (dLGN) of the rat were visualized by anterogradely transported horseradish peroxidase following injections in the optic tract. The morphological findings confirm the two types of retinal axons previously suggested by Golgi investigations. In the caudal third of the dLGN type 2b axons, with small dense clusters of boutons, are the only representatives of retinal fibres seen. In the rostral two thirds they are intermingled with the larger type 2a terminals, but tend to accumulate laterally, adjacent to the optic tract. This study supports the concept that large retinal ganglion cells probably give rise to 2a axons that may represent a Y-like channel, whereas 2b axons are derived from small ganglion cells, and may relay a W-like pathway.
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New prodrugs of acyclic nucleosides with antiviral activity.
More than 130 acyclic purine and pyrimidine nucleoside derivatives have been synthesized. Structure-activity relationships among a selected group of 6- and 9-substituted guanine derivatives will be discussed. By introduction of secondary aliphatic (e.g. isopropyl or secondary butyl) ether groups into acyclic nucleosides such as aciclovir and ganciclovir new lipophilic prodrugs with modified physical and improved pharmacokinetic properties have been obtained. Several compounds with isopropylether groups in the side-chain and/or in the 6-position (among these the 6-deoxy derivative Hoe 602) of the purine moiety displayed excellent antiviral activity when tested in vivo against herpes simplex virus type 1 infection in mice.
Acyclovir↗
[Brain morphology of Microtus brandti (Radde, 1861) and Alticola argentatus semicanus (Allen, 1924) (Rodentia, Cricetidae). Results of the Mongolian-German biological expeditions since 1962, No. 189)].
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Neurons in the basal forebrain complex of the rat: a Golgi study.
Several types of neurons are coexistent in the basal forebrain nuclear complex of the rat. In the medial septum and vertical limb of the diagonal band 3 classes of neurons occur which are characterized by varicose dendrites. In the horizontal limb of the diagonal band neurons with smooth dendrites and those with varicose dendrites are intermingled. We found 3 classes of neurons in the nucleus preopticus magnocellularis. A giant type with smooth and varicose dendrites occurs in this nucleus, but also in the substantia innominata. In the substantia innominata-nucleus basalis complex 4 classes of neurons with varicose dendrites and 2 classes with spiny dendrites have been observed. Our findings suggest that the nucleus of the vertical limb of the diagonal band forms a unit with the nucleus septi medialis, but is separated from the nucleus of the horizontal limb of the diagonal band by different neuronal composition. The nucleus preopticus magnocellularis is a separate nuclear structure characterized by a content of neurons different from those in the horizontal limb of the diagonal band and in most components also from the substantia innominata-nucleus basalis complex. There is some evidence that the cholinergic neurons have to be searched among those with varicose dendrites.
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