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E Trenkner

Publications and source records attributed to E Trenkner.

At least 37 records · Page 2Linked to original sources
PubMed1988

Progressive loss of neuronal src protein in postnatal weaver and staggerer cerebellum.

Two forms of the c-src protein-tyrosine kinase, pp60c-src, are detectable in the central nervous system. One form pp60+, appears to be exclusively expressed in neurons and is characterized by insertion of 6 amino acids compared to its non-neuronal counterpart, pp60. These 2 proteins were studied in the mutant mouse strains weaver and staggerer with postnatal loss of cerebellar granular neurons. We found a continuous postnatal decline of the neuronal form of pp60c-src, pp60+, in the cerebellum of both mutants concomitant with the degeneration of cerebellar granule cells. This indicates that granular neurons provide the main source for pp60+ in the cerebellar cortex.

Animals↗
PubMed1987

Regional differences in cytoarchitecture of the weaver cerebellum suggest a new model for weaver gene action.

This paper examines the structure and cytoarchitecture of the cerebellum of the weaver mutant mouse with particular emphasis on regional differences along the mediolateral and anterior-posterior axes. We have uncovered several, previously undescribed features of the weaver cerebellar phenotype. Perhaps the most dramatic example of our findings is the severe disruption of the folial structure of the hemispheres of the weaver cerebellum. A dorsal overgrowth of tissue occurs in the hemispheres that forms a finger-like projection superficial to an atrophic but structurally more normal cerebellar mass underneath. While this folial abnormality is most evident in the homozygote (wv/wv) the antecedents of its appearance are already apparent in the heterozygote (+/wv). At the level of the cytoarchitectonics of the mutant brain, we find substantial variation in the positioning, numbers and density of both Purkinje and granule cells. As a whole, Purkinje plus Golgi II cell numbers are down by over 40%, but this reduction occurs almost exclusively in the medial half of the cerebellum. The hemispheric region contains a nearly normal number of cells per sagittal section (although their positions are predominantly incorrect). The granule cells also show numerical variation; they are nearly absent at the midline, but a substantial number of them survive in the lateral cerebellar cortex. In the paraflocculus, for example, granule cells can be observed in a modest internal granule cell layer as late as 38 postnatal days. These results are discussed in terms of a model of wv gene action in which we propose that the effect of the mutation is a general disruption of cellular distribution in the cerebellar cortex, affecting both Purkinje and granule cells and beginning prenatally.

Age Factors↗
PubMed1987

Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury.

The neuroexcitotoxin kainate has been used as a selective lesioning agent to model the etiology of a number of neurodegenerative disorders. Although excitotoxins cause susceptible neurons to undergo prolonged or repeated depolarization, the proximate metabolic pathology responsible for neuronal necrosis has remained elusive. We report here that kainate-induced death of cerebellar neurons in culture is prevented by inhibiting the enzyme xanthine oxidase, a cellular source of cytotoxic superoxide radicals (O2-.). Moreover, neurons are also protected from excitotoxin-induced death by the addition to the culture medium of either superoxide dismutase or mannitol, which scavenge superoxide and hydroxyl radicals, respectively, or serine protease inhibitor, which forestalls formation of xanthine oxidase. These findings indicate that excitotoxin-induced neuronal degeneration is mediated by superoxide radicals generated by xanthine oxidase, a mechanism partially analogous to that proposed for tissue damage seen upon reperfusion of ischemic tissues.

Allopurinol↗
PubMed1986

Probable identity of NILE glycoprotein and the high-molecular-weight component of L1 antigen.

We report here that anti-L1 antiserum, raised against material from embryonic brain, and anti-NILE antiserum, raised against purified NILE (nerve growth factor-inducible large external) glycoprotein of PC12 cells, immunoprecipitate from PC12 cells material of the same apparent molecular weight (230 kilodaltons) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Furthermore, each of these immune reagents has the capacity to clear from a PC12 cell extract all of the 230-kilodalton antigen recognized by the other antiserum. Finally, in immunohistochemical staining of developing cerebellum the two antisera exhibit very similar staining patterns. We suggest that the NILE glycoprotein and the high-molecular-weight component of L1 antigen are closely related molecules, and probably the same.

Adrenal Gland Neoplasms↗
PubMed1986

Defective development of the thymus and immunological abnormalities in the neurological mouse mutation "staggerer".

The autosomal recessive mouse mutation "staggerer" (sg/sg), located on chromosome 9, has been recognized as a neurological mutant because of movement abnormalities and defective cerebellar development. We show here that the sg/sg mutation not only affects the development of the cerebellum, but also causes developmental and regulatory changes of the immune system: We observed, on gross inspection, a marked delay in the development of sg/sg thymus, generally enlarged lymph nodes, and undersized spleens. When immunized with SRBC, the sg/sg mouse generated, in normal proportions, helper T-cells in vivo and antibody-forming B-cells in vitro; however, a delay in terminating the response and a deficiency in generating suppressor cells was noted. This suggests the existence of a defect in regulatory feedback mechanisms. The marked delay in the growth of the thymus gland was associated with the prolonged existence of cell-surface carbohydrate patterns characteristic of immature thymocytes. The prolonged expression of embryonal cell-surface phenotypes was observed on the surface of cerebellum and thymus (and, to some extent, spleen) but not in cells from other organs.

Animals↗
PubMed1984

Is cerebellar granule cell migration regulated by an internal clock?

We have studied the time course of migratory behavior of cerebellar granule cells in the microwell tissue culture system. [3H]Thymidine served as a marker for particular granule cell generations. When cultured 4 hr after [3H]thymidine injection for 6 days in microwell cultures, labeled granule cells were seen to migrate along fiber bundles expanding between reaggregates called "cables" for 3 to 4 days. After 5 and 6 days in vitro the percentage of labeled non-migrating cells found in clusters in reaggregates and on cables increased considerably. Whereas unlabeled cells continued to migrate. Comparable results were obtained when granule cells developed in vivo for various times after label and their developmental state was determined in vitro. Cells from cerebellar populations labeled 1 to 4 days before culture maintained their ability to migrate in vitro, even after granule cells had entered the internal granule cell layer. In contrast, the percentage of migrating cells labeled 5 and 6 days before culture was reduced significantly. The results suggest that the time span of granule cell migration is predetermined intrinsically rather than by external signals.

Animals↗
PubMed1983

Development-dependent regulation of N-acetyl-beta-D-hexosaminidase of cerebellum and cerebrum of normal and staggerer mutant mice.

Distinctive activities of various glycosidases were expressed in the cerebellum and cerebral cortex of mice during their development. In particular, N-acetyl-beta-D-hexosaminidase (EC 3.2.1.30) appeared to be developmentally regulated. A transient peak of enzyme activity at postnatal day 7 was characteristic for the cerebellum, whereas the activity in the cerebral cortex gradually increased through the 1st postnatal month and was maintained at a high level of activity throughout adulthood. The regulation of N-acetylhexosaminidase activity in the developing cerebellum of the staggerer mouse deviated clearly from enzyme activities in the wild-type, whereas the activity pattern in the staggerer cerebral cortex remained unaffected. In experiments mixing wild-type and staggerer cerebellum homogenates, the specific activity was additive. Thus, involvement of inhibitors or activating molecules can be excluded. This developmentally controlled regulation or disregulation in staggerer appears to be enzyme specific, sine beta-glucosidase, alpha-glucosidase, and beta-galactosidase did not exhibit such a pattern in either normal or staggerer mice. In the mutation weaver that, like staggerer, loses the majority of its cerebellar granule cells, N-acetyl-beta-hexosaminidase activity of the cerebellum was not elevated, indicating a specific defect in staggerer rather than a general effect on lysosomal enzymes due to cell death.

Aging↗
PubMed1981

Changes in particulate neuraminidase activity during normal and staggerer mutant mouse development.

The activity of particulate neuraminidase (sialidase, EC 3.2.1.18) in wild-type mice and the neurological mutant Staggerer was studied during development. Peak activity of this enzyme was observed at postnatal day 3 (P3) in three tissues of normal mice: cerebellum, cerebrum, and liver. In Staggerer, however, neuraminidase peak activity was observed at P27 in the cerebellum, whereas the activity was close to normal in Staggerer cerebrum and liver. Activities of the other glycosidases in Staggerer (alpha-glucosidase (pH 3.7), alpha-glucosidase (pH 6.0), N-acetyl-beta-hexosaminidase, beta-glucosidase, and beta-galactosidase) did not show significant variation compared with wild-type at P27 in any of the three tissues. This indicates that the late activity peak of particulate neuraminidase activity in the Staggerer cerebellum is neuraminidase-specific and not due to a general increase of lysosomal enzymes.

Aging↗
PubMed1977

Microbial carbohydrate specific antibodies distinguish between different stages of differentiating mouse cerebellum.

High titered anticarbohydrate antibodies were used to identify cell surface carbohydrates during different stages in histogenesis of mouse cerebellum in a micro tissue-culture system which mimics selected features of in vivo cerebellum development. Blockage of fiber formation within the first few days in vitro and inhibition of cell migrations by carbohydrate-specific antibodies served as an assay system for possible contributions of surface carbohydrates to the behavior of developing cerebellar cells. Microbial strains were selected on the basis of carbohydrate structures of their cell wall antigens, and anticarbohydrate antibodies were raised against treated whole bacteria and yeast in rabbits. We found that antibodies to mannan were active at all stages of development tested (embryonic day 13, E13; the day of birth, PO; and postnatal day 7, P7). Antibodies to sialic acids prepared against strains B and C of Neisseria meningitidis distinguish different subterminal structures: anti-B reacted with E13 and PO cerebellar cells, and anti-C mostly with cells older than P7. Antifetuin antibody recognized E13 and PO but not P7 cell populations. Pneumococcus C strain R36A-specific antibodies were effective only after coating cells to C type carbohydrate before application of the antibody. The results demonstrate that antimicrobiol carbohydrate antibodies cross-react with mammalian cell surface carbohydrate structures and therefore can be used as a powerful tool in tissue culture to analyse those structures which might control cell behaviors pertinent to cerebellar development.

Animals↗
PubMed1977

Histogenesis of mouse cerebellum in microwell cultures. Cell reaggregation and migration, fiber and synapse formation.

A microwell culture system was developed for analysis of cell movements and interactions during nervous system histogenesis. Cells from trypsinized 7-day-old mouse cerebellum reaggregated within hours into clusters which later developed interconnections consisting of either sheets of migrating cells and cell processes or cables of fiber bundles with cells migrating along their surfaces. Granule cells in several stages of differentiation, basket and/or stellate neurons, some larger neurons, and two types of neuroglial cells were identified in reproducible, nonrandom patterns by scanning and transmission electron microscopy. Axonal and dendritic processes, both with growth cones, and numerous synapses were generated in vitro.

Animals↗
PubMed1975

Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies.

Anti-idiotypic antibodies have been used to mimic antigen in the mouse antiphosphorylcholine response in order to investigate the induction of precursors of antibody-forming cells. We have shown that interaction of anti-idiotype antibody with receptor antibody molecules induces the formation of antibodies that are specific for phosphorylcholine and carry the idiotypic determinants. This induction is dependent on the recognition of carrier determinants on the anti-idiotype antibody by helper T cells. We conclude that receptor antibody molecules on the surface of the precursors of antibody-forming cells deliver the antigenic signal for the induction of these cells.

Animals↗