Search PubMed⌕ Search

Biomedical subjects

G Danscher

Publications and source records attributed to G Danscher.

At least 91 records · Page 5Linked to original sources

The effect of low-level toluene exposure on the developing hippocampal region of the rat: histological evidence and volumetric findings.

With the intention of investigating possible morphological alterations effected by toluene in the developing CNS, rat pups were exposed to 100 ppm and 500 ppm of atmospheric toluene from postnatal day 1 until sacrifice at postnatal day 28, when the hippocampal region (area dentata, Ammon's horn, subiculum) was examined light microscopically and alterations in the volumes of the layers of the subdivisions were determined. The layers of Ammon's horn and the subiculum were not affected qualitatively or quantitatively by the 500 ppm exposure. Within the area dentata, the volume of the granule cell layer was 6% smaller in animals exposed to 100 ppm and 13% smaller in animals exposed to 500 ppm than they were in controls. The volumes of the hilus, which is a terminal field of granule cell axons, and the commissural-associational zone of the dentate molecular layer, which is the terminal field of the hilar projection to the granule cells, were smaller (12% and 19%) in animals exposed to 500 ppm than they were in controls. Argyrophilic cells were found in the granule cell layer of all animals exposed to 500 ppm. Pronounced granule cell degeneration was found in one animal exposed to 500 ppm. The granule cell layer of animals exposed to 100 ppm appeared qualitatively normal. The alterations reported here support the few earlier reports of morphological alterations in the CNS of adult laboratory animals. Effects of toluene similar to those described, that is alterations in specific neuron populations and their afferent and efferent terminal fields may complement changes in neurophysiology and behavior that have been observed in prenatally and perinatally exposed rodent pups. Causal relationships, however, remain to be elucidated.

Animals↗

In situ binding of bouton zinc reversibly disrupts performance on a spatial memory task.

Neurons with zinc in the presynaptic vesicles innervate much of the telencephalon, but the functional significance of the vesicular zinc has never been established. The present work shows that reversible binding of zinc by drug infusion into the hippocampus produces a time-locked and selective disruption of hippocampal-dependent spatial-working memory. A role for vesicular zinc in neurotransmission or neuromodulation is implied.

Animals↗

Traces of mercury in organs from primates with amalgam fillings.

In order to trace possible accumulations of mercury, three vervet monkeys received occlusal amalgam fillings, three others maxillary bone implants of amalgam, and three untreated monkeys served as controls. One year later all animals were sacrificed by transcardial perfusion with glutaraldehyde. Tissue sections from different organs were subjected to silver amplification by autometallography and analyzed at light and electron microscopical levels. It was found that amalgam fillings (total, 0.7-1.2 g) caused deposition of mercury in the following tissues: spinal ganglia, anterior pituitary, adrenal, medulla, liver, kidneys, lungs, and intestinal lymph glands. In monkeys with maxillary silver amalgam implants (total, 0.1-0.3 g), mercury was found in the same organs except for liver, lungs, and intestinal lymph glands. Organs from the three control animals were devoid of precipitate. To evaluate whether silver released from the corroding amalgam fillings added to the staining pattern, tissue sections were exposed to potassium cyanide prior to being autometallographically developed. This treatment removes all traces of silver, leaving mercury sulfide accumulation untouched. By comparing sections that had been exposed to cyanide with untreated parallels no difference was seen in the pattern confirming that mercury was the only catalyst present in the tissue. These results strongly support what has been suggested previously that dental fillings in primates cause absorption of mercury released from amalgam fillings through lungs and intestinal tract, and that depending on exposure mercury is distributed to most organs and will eventually be found in the central nervous system. The present data also show that silver released from the corroding filling is not absorbed.

Animals↗

Labeling of the neurons of origin of zinc-containing pathways by intraperitoneal injections of sodium selenite.

Intraperitoneal injections of sodium selenite result in the formation of zinc-selenium complexes in zinc-containing axonal boutons ("Timm stainable boutons"), and the zinc-selenium precipitate can be rendered visible in histological sections by silver enhancement. In this work we present evidence, in the rat, that zinc-selenium precipitates formed in vivo after intraperitoneal injections of sodium selenite are translocated by colchicine-sensitive retrograde transport to neural perikarya when animals are allowed to survive 12-24 h after the selenite administration. Silver enhancement renders the perikaryal precipitates visible and thus demonstrates the perikarya of all zinc-containing neurons in the CNS simultaneously. Large populations of zinc-containing neurons identified by the method are found in layers II, III, and VI of all neocortical areas, in the superficial and deep layers of the prepyriform areas and, with a high degree of regional differentiation, in the retrosplenial, entorhinal, para- and presubicular cortices, the hippocampal formation and the amygdaloid complex. Zinc-containing cells were absent from the caudate-putamen, nucleus accumbens and septal complex. Labeled zinc-containing cells are absent in non-telencephalic parts of the brain. The findings indicate that the zinc-containing circuitry of the brain mainly serves in telencephalic information processing.

Animals↗

Zinc-containing neurons in hippocampus and related CNS structures.

Recent advances in metallohistochemistry have substantiated the identification of a distinct class of neurons in the brain, the zinc-containing neurons. These neurons sequester peculiar amounts of zinc in their presynaptic boutons and show both high-affinity uptake and calcium- and impulse-dependent release of the cation. It is thought that the zinc may act to stabilize the storage of certain macromolecules in presynaptic vesicles, but there is also mounting evidence that zinc released from vesicles can produce a broad spectrum of neuromodulatory effects upon target cells. Zinc-containing neurons are found predominantly in limbic and cerebrocortical regions, and a possible role of these neurons in the modification of synaptic strength is considered.

Animals↗

Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam.

Fourty-three patients with oral mucosal lesions were divided into 3 groups based on the relationship between lesions and amalgam restorations. Group I consisted of patients with contact lesions confined to mucosal areas in contact with amalgam fillings. Group II patients had lichen planus lesions exceeding the area of contact with an amalgam filling and Group III comprised patients with lichen planus lesions without relation to amalgam fillings. Biopsies were embedded in epon and subjected to autometallography in order to demonstrate a possible accumulation of mercury in the affected mucosa. In 20 our of 21 patients in Group I, 4 of 11 patients in Group II and 4 of 11 patients in Group III, mercury was found in the lysosomes of macrophages and fibroblasts. In Group I the number of cells loaded with mercury was much higher than in Group II and in particular Group III. In the latter groups autometallographically demonstrated mercury was found almost exclusively in macrophages. Nineteen biopsies taken from patients with normal mucosa served as controls. Ten had occlusal (Group IV) and seven buccal fillings (Group V). The biopsies from the latter group were taken from areas opposing amalgam restorations. Two patients had no amalgam fillings (Group VI). The histochemical technique showed that three biopsies in Group IV (occlusal fillings only) and two in Group V (opposing buccal fillings) contained traces of mercury in the juxtaepithelial connective tissue. The silver enhanced mercury was found in macrophages. The two controls (Group VI) without amalgam fillings were devoid of precipitates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Amygdaloid efferents through the stria terminalis in the rat give origin to zinc-containing boutons.

Many regions of the basal forebrain are innervated by zinc-containing axonal boutons. In the present work, the lesion/degeneration method, coupled with histochemical staining for zinc-containing boutons, was used to determine the origins and efferent pathways of these zinc-containing projections to the basal forebrain. Knife cuts of the stria terminalis or extensive electrolytic lesions of the amygdala resulted in the bleaching of the staining for zinc (Timm stain) and terminal degeneration (Fink-Heimer method) ipsilaterally in the following areas: granule cell layer of the accessory olfactory bulb, shell of nucleus accumbens, bed nucleus of the stria terminalis, striohypothalamic nucleus, retrochiasmatic area, ventromedial hypothalamic nucleus (in the cell-sparse shell), medial tuberal nucleus, terete hypothalamic nucleus, and ventral premammillary nucleus. Small lesions made with ibotenic acid in the posteromedial part of the amygdalohippocampal area caused bleaching of the stain for zinc in the accessory olfactory bulb, in the medial zone of the bed nucleus of the stria terminalis, and in the ventral premammillary nucleus. Lesions in either the ventral subiculum or the anterolateral part of the amygdalohippocampal area caused bleaching in the ventromedial hypothalamic nucleus. Lesions in the hippocampus or in the neocortex did not produce bleaching of the stain for zinc in the above-mentioned terminal fields. The present results agree with previous studies on amygdaloid efferents and suggest that neurons in the amygdalohippocampal area and, possibly, in the ventral subiculum give origin to zinc-containing boutons.

Amygdala↗

Evidence from dithizone and selenium zinc histochemistry that perivascular mossy fiber boutons stain preferentially "in vivo".

This paper describes a perivascular staining pattern that is obtained when dithizone or sodium selenite are used to label zinc intravitally. Our observations indicate that the perivascular staining is a result of zinc labeling in mossy fiber boutons adjacent to capillaries and suggest that there might be a special blood brain barrier in the mossy fiber regions.

Animals↗

Distribution of dietary mercury in a dog. Quantitation and localization of total mercury in organs and central nervous system.

An Alsatian dog which had been fed fish contaminated with methyl mercury for 7 years was examined after its death at the age of 12, 4 years after the exposure to methyl mercury had ceased. Two dogs of the same age and breed served as controls. In the exposed dog, mercury was found in all of the organs examined; the highest concentrations were found in the kidneys, and the lowest in the gastrointestinal tract and skeletal muscles. In the central nervous system (CNS) the mercury was fairly uniformly distributed, with 93% in the inorganic state, whereas the skeletal muscles contained approximately 30% inorganic mercury. This demonstrates time-dependent demethylation and suggests a variation in the rate from one type of tissue to another. At the time of death, the mercury level in the dog was still falling. In the control dogs, detectable amounts (0.01 mg kg-1) of mercury were only found in the kidney and liver. The distribution of mercury was determined by a histochemical method (autometallography) for locating mercury in tissue sections. Sections from autometallography of the central nervous system showed large deposits of mercury in all areas of the cerebral hemispheres, the brainstem and the spinal cord, including nerve cells, astrocytes, microglial cells and vessel walls. The granular layer of the cerebellar hemispheres was especially loaded, while only a few granules were present in the Purkinje cells. In the leptomeninges the vessels and the macrophages were heavily encrusted. High amounts of histochemically demonstrable mercury were observed in the liver, thyroid gland and kidney. In the control dogs, all the organs examined were practically devoid of deposits.

Animals↗

Silver enhancement of tissue mercury: demonstration of mercury in autometallographic silver grains from rat kidneys.

The autometallographic silver enhancement method has been applied increasingly to detect trace amounts of mercury in preparations of biological tissue. It has, however, been difficult to establish the presence of a core of mercury within the silver grain by direct methods such as energy dispersive X-ray analysis. In the present work, a sample of autometallographic silver grains was prepared from kidneys of rats exposed to mercury in the drinking water. Frozen sections from the kidneys were silver-enhanced and subsequently all organic material was removed by enzymatic digestion. The remaining pellet of silver grains was analyzed by proton-induced X-ray emission (PIXE) and mercury was demonstrated in an amount of 0.1-0.5% compared to silver. In addition, it was demonstrated that two pools of catalytic mercury compounds exist, probably corresponding to sulfide- and selenium-bound mercury.

Animals↗

Dose-dependent bimodal effect of low-level lead exposure on the developing hippocampal region of the rat: a volumetric study.

The hippocampal region is known to accumulate experimentally applied and environmentally occurring lead and to be implicated in lead-induced behavioral deficits. With the intention of investigating morphological changes resulting from the lower range of exposures that produce behavioral alterations in laboratory animals, the volumes of hippocampal components were determined in groups of rats exposed from postnatal days 0-21 to different concentrations of lead through the maternal water supply (initially 109 ppm, subsequently replicated with 109, 218, 436 and 872 ppm). Significant effects were found in the mossy fiber zone, the granule cell layer and the commissural-associational zone of the dentate molecular layer of the group exposed to 109 ppm lead and the pyramidal cell layer of regio inferior (CA3) of Ammon's horn in the group exposed to 218 ppm lead. These results provide evidence that lead primarily affects newly formed neuronal components. In contrast to the results of previous studies, which used larger exposures to lead, the components affected in the group exposed to 109 ppm increased in volume. In addition, no significant effects were observed in the groups exposed to 436 and 872 ppm. Based on these findings and additional evidence from the literature, it is concluded that lead has a dose dependent bimodal influence on developing hippocampal components. While the volumetric changes related to lead were of the same magnitude and direction in the initial and replication studies, the absolute volumes of the affected hippocampal components were different. The differences in "baseline" values in the two studies are more likely related to differences in prenatal conditions.

Animals↗

Quantification of vesicular zinc in the rat brain.

By means of the Neo-Timm method it has recently been shown that zinc is present in a fraction of the round clear synaptic vesicles of certain boutons located primarily in telencephalic structures (Pérez-Clausell and Danscher 1985). It is believed that this zinc belongs to a fraction of the total brain zinc which is histochemically active (Frederickson and Danscher 1988) in that it can be visualized by means of e.g. the Neo-Timm and selenium methods (autometallography). The present study is based on the suggestion that the autometallographically developed zinc patterns represent a histochemical quantitative expression of this fraction of the total brain zinc. The different colours of the zinc pattern reflect local variations in the concentration of zinc containing vesicles. Large boutons with a high content of stained vesicles will show up darkly because of fusion of adjoining silver grains while smaller boutons with fewer zinc containing vesicles give rise to yellow staining of various shades. We have exploited this difference in staining of pattern by applying computerized optic densitometry to light microscopic sections treated according to the Neo-Timm and the selenium methods, respectively.

Animals↗

Zinc-containing fiber systems in the cochlear nuclei of the rat and mouse.

Zinc-containing neurons are cells which sequester zinc in the vesicles of their axonal boutons; such zinc-containing fiber systems have been previously shown to innervate many limbic and cerebrocortical brain regions. The present study of rats and mice shows that zinc-containing axons also innervate the cochlear nuclei, forming two morphologically-distinct projection systems. One zinc-containing pathway innervates the molecular stratum of the dorsal nucleus, supplying a diffuse, even band of neuropil staining throughout the stratum. The other pathway projects sparsely to the various small cell (granule cell) regions of the nuclei where the zinc-positive elements form scattered clusters and threads of bouton-like puncta amidst the granule neuron somata. Preliminary observations indicate that the pattern is the same in the cat as in the rat and mouse.

Animals↗

Hippocampus and dentate area of the European hedgehog. Comparative histochemical study.

The hippocampal formation in the European hedgehog was examined with acetylcholinesterase (AChE) histochemistry and catecholamine histofluorescence in order to define the normal distribution of septohippocampal fibers and noradrenergic fibers, respectively, as well as to compare these inputs with the hippocampal cytoarchitecture as revealed with Nissl stain. In addition, alterations in the histochemical appearance following septohippocampal denervation were examined. Although the overall pattern of AChE-positive and noradrenergic fibers is similar to that observed in other mammals, some striking variations were observed, particularly within the dentate area. Thus, except for a heavily stained supragranular band, the AChE activity of the molecular layer is uniformly low without any obvious lamination, contrasting with the situation in most other mammalian species. The noradrenergic innervation of the dentate area showed the same density of fibers in the molecular layer and hilus, a pattern differing strikingly from the predominance of noradrenergic fibers in the hilus of other mammalian species. Such variations may reflect greater phylogenetic diversity in diffuse modulatory connections as compared with more precise topographical pathways.

Acetylcholinesterase↗