Biomedical subjects

D Koczyk

Publications and source records attributed to D Koczyk.

8 recordsLinked to original sources

PubMed2000

Long-term microglial and astroglial activation in the hippocampus of trimethyltin-intoxicated rat: stimulation of NGF and TrkA immunoreactivities in astroglia but not in microglia.

In the present study we investigated the microglial and astroglial response after trimethyltin (TMT) exposure over a prolonged period of time. Male Wistar rats were given a single dose of TMT (8 mg/kg, i.p.) and survived 4, 7, 21, 60 and 180 days after the administration of the toxin. Histochemistry (Griffonia simplicifolia lectin staining) and immunocytochemistry for GFAP were applied to identify micro- and astroglial cells, respectively. To assess the trophic response of glial cells (NGF and TrkA expression), single or double staining experiments were performed. In addition, the biochemical evaluation of GFAP and NGF were carried out at chosen timepoints using immunoblotting technique and ELISA, respectively. The main findings of our study were as follows. (1) A protracted activation of microglia (at least up to 2 months posttreatment). (2) A long-lasting expression of GFAP immunoreactivity (at least up to 6 months posttreatment) and a steady increase in GFAP content (at least up to 2 months posttreatment). (3) The appearance of enormously enlarged, round-shape astrocytes exclusively localized to CA1 and observed 2 months posttreatment. (4) The stimulation of NGF and TrkA expression in reactive astrocytes. (5) The strongest activation of micro- and astroglia coincided with the most prominent neurodegeneration in the hippocampus, i.e., in CA4/CA3c and CA1. It is tempting to assume that the activation of glial cells in the hippocampal areas particularly vulnerable to TMT may affect neuronal fate after neurotoxic insult.

Animals↗

PubMed1998

Spatiotemporal changes in hippocampal NMDA receptor binding as a consequence of trimethyltin neurotoxicity in the rat.

In the present study we examined the presumable changes in the distribution of N-methyl-D-aspartate (NMDA) receptors in the hippocampus of rat exposed to a potent neurotoxic drug, trimethyltin (TMT). Using in vitro receptor binding autoradiography, [3H]MK801 labelling was determined at 7, 14, 21, 30 and 60 days after treatment with TMT (single dose of 8 mg/kg, i.p.) in various hippocampal areas thought to be affected by the neurotoxin. At 21-60 days after exposure, a decrease in receptor binding was observed in CA1 hippocampal subfield (10-20%, P< 0.05). A reduction in binding density also occurred in CA4/ CA3c, where labelling vanished completely at longer times. In the molecular layer (ML) of the dentate gyrus (DG), however, 16-37% (P<0.05) increase in receptor binding was found at 14-60 days postexposure. These results suggest that exposure to TMT leads to an altered topography of NMDA receptor density sites in the rat hippocampus. Dynamics of the reduction in receptor binding in CA4/CA3c and CA1 followed the development of the well-known degenerative effects induced by the neurotoxin. In contrast, the enhanced binding density in the ML of the DG may be a part of a mechanism of plastic response of granule cells to denervation/reinnervation.

Animals↗

PubMed1996

Trimethyltin-induced plastic neuronal changes in rat hippocampus are accompanied by astrocytic trophic activity.

Partial deafferentation of the hippocampus due to trimethyltin (TMT) intoxication has been reported to induce plastic rearrangements of neuronal elements but the factors that direct these responses are unknown. To assess the possible involvement of nerve growth factor (NGF) in the phenomenon we evaluated the presumable changes in the expression pattern of NGF immunoreactivity (NGF-IR) in rat hippocampus 21 days after administration of TMT (8 mg/kg, i.p.) when reactive changes are fully developed. Immunolabelling for TrkA known to mediate biological effects of NGF and for GFAP to identify astroglial cells as a one of presumed source of postinjury produced factors was carried out on adjacent sections to establish the relation between expression of these proteins. In control hippocampus NGF-IR and TrkA-IR were localized in neurons and/or neuropil. After exposure to TMT remarkable non-neuronal expression of both proteins was observed. The distribution pattern of NGF, TrkA and GFAP overlapped suggesting that reactive astrocytes may not only produce NGF but also may become responsive to this neurotrophin. Zones of extensive NGF and TrkA astroglial expression corresponded to areas of axonal-dendritic rearrangements reported earlier. The data suggest that astroglia-derived trophic activity may be involved in neuronal plastic events associated with treatment with TMT.

Animals↗

PubMed1996

Axonal accumulation of p75NTR and TrkA in the septum following lesion of septo-hippocampal pathways.

Septal cholinergic neurones depend on trophic support by nerve growth factor (NGF) which can rescue them from injury-induced degeneration. Since NGF exerts its effects via p75NTR and TrkA receptors coexpressed in vast majority of these neurones and down-regulated without NGF treatment after injury, in this study we aimed to examine how does the lesion to the cholinergic tracts affect distribution of both types of receptor proteins in damaged fibres. Early changes (two and seven days) were examined immunocytochemically within the septum and supracallosal stria after unilateral lesion to the supracallosal area and cingulum transecting some septal cholinergic efferents. We found accumulation of p75NTR and TrkA immunoreactive material (so-called "pile-up") within axonal segments of distended appearance proximal to the transection at two days postlesion and its translocation towards cell bodies seven days postsurgery. We observed p75NTR pile-up to be more intense than TrkA, which may indicate different cellular concentrations of both receptors. Receptor pile-up resembled acetylcholinesterase pile-up reported previously, suggesting a common response mechanism involving axonal transport disturbances.

Acetylcholinesterase↗

PubMed1996

How does trimethyltin affect the brain: facts and hypotheses.

Trimethyltin, an organic compound of tin, is a potent neurotoxicant of a mechanism of action yet to be uncovered. The neuropathological findings that trimethyltin causes selective hippocampal damage with several unique features, highly reminiscent of Ammon's horn sclerosis as a final result, have raised the possibility that there is a link between trimethyltin neurotoxicity and other degenerative events for which an imbalance between neuronal inhibition/excitation has been proposed. However, there still exists a whole catalog of issues which await clarification. One of the greatest importance is how does trimethyltin reach the critical sites within the brain and what are they? Available data concerning the long-term consequences related to trimethyltin neurotoxicity are also far from being completed. This review summarizes current data from in vitro and in vivo studies on neurotoxic effects of trimethyltin. Several hypotheses on mechanisms that may lead to neuronal death induced by the toxin are presented.

Animals↗

PubMed1995

Bilateral gliosis in unilaterally lesioned septohippocampal system: changes in GFAP immunoreactivity and content.

Unilateral damage to the lateral fimbria led to a bilateral gliosis in the septum and hippocampus. The gliosis was manifested by an increase in GFAP staining, accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+) cells and GFAP content; the latter however was not visible in the contralateral septum. In general, the contralateral reaction appeared weaker than the ipsilateral one. The pattern of contralateral increase in GFAP-immunoreactivity (IR) matched almost exactly that observed on the ipsilateral side in the hippocampus (the most evident increase was seen in the oriens and pyramidal layers of cornu Ammonis 3 and in polymorphic area of gyrus dentatus). In the septum the bilateral increase in GFAP-IR was mainly visible in the dorsolateral quadrant of the structure; however in the ipsilateral side it spread over the whole half of the structure. The astrocytic responses in the septum and hippocampus were not equivalent: they differed mainly with regard to the increase of GFAP(+) cells (over 300% of control in the anterior part of the septum and only about 120% in the dorsal hippocampus). The differences between the percentage increases of other gliotic indices: GFAP-IR and GFAP content. Various possibilities that may account for the occurrence of contralateral gliosis are discussed, the most plausible being the contribution of interhemispheric and intraseptal links and the action of some diffusible agents. We suggest that bilateral gliosis may have an impact on compensatory postlesion processes, possibly by providing trophic support to impaired neurons.

Animals↗

PubMed1994

Differential response of microtubule-associated protein 2 (MAP-2) in rat hippocampus after exposure to trimethyltin (TMT): an immunocytochemical study.

Several neurotoxins induce changes in microtubule-associated protein 2 (MAP-2), the cytoskeletal protein primarily and highly enriched in the dendritic compartment of neurones. The present study aimed to investigate the fate of MAP-2 after administration of trimethyltin (TMT), an environmental neurotoxin. An immunocytochemical staining was performed in the hippocampus, known to be the most vulnerable brain region after TMT exposure. Prolonged survival time (21 days) following i.p. injection of a single dose of TMT (8 mg/kg) led to a considerable changes in intensity and pattern of distribution of MAP-2 immunoreactivity within the structure. A significant decrease in the staining was observed in the hippocampus proper especially in CA4/CA3 and CA1 subfields. This decrease was correlated with the severity in pyramidal cell loss previously reported by others. On the contrary, an increased density of MAP-2 immunostained dendrites was found in the molecular layer of dentate gyrus. Since TMT has been recognized as an agent damaging not only the hippocampus but also other limbic structures, the latter result might be interpreted in terms of postsynaptic changes due to hippocampal deafferentation.

Animals↗

PubMed1993

Differential effects of GM1 ganglioside treatment on glial fibrillary acidic protein content in the rat septum and hippocampus after partial interruption of their connections.

The glial fibrillary acidic protein (GFAP) content was investigated using immunoblotting techniques in the septum and hippocampus of the rat after bilateral lateral fimbria transection. Seven days after surgery GFAP content increased significantly both in the septum (140% of control) and hippocampus (120% in dorsal, the less denervated, and 145% in the most denervated ventral part), indicating the occurrence of reactive gliosis. The GM1 treatment caused statistically significant attenuation of GFAP increment in all hippocampal parts. In contrast, GM1 treatment has no influence on the increase of GFAP content in the septum. Results suggest a differential effect of GM1 on the two gliotic reactions formed as a consequence of the lesion at the level of the source of innervation (septum) and the target (hippocampus).

Animals↗