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  • 1
    ISSN: 1432-0568
    Keywords: Cerebellar graft ; Deep cerebellar nuclei ; Neurological mutant mice ; “Purkinje cell degeneration” (pcd)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In transplanting embryonic cerebellar grafts to the cerebellar cortex of “Purkinje cell degeneration” (pcd) mutant mice to replace missing Purkinje cells (PC), donor PC leave the graft and migrate to the molecular layer of the host. However, PC axons do not always reach the deep cerebellar nuclei of the host, which would be a key element in restoring much of the necessary inhibitory cortico-nuclear projection associated with normal cerebellar function. Rather, grafted PC axons often innervate a region containing deep cerebellar nuclei neurons inside the transplant, while the perikaryon migrates to the host molecular layer. In the present study, aimed at re-establishing a PC innervation of the deep nuclei, we implanted E12 cerebellar cell suspensions intraparenchymally to the deep cerebellar mass of the hosts. The development of grafted PC was monitored with 28-kDa calcium-binding protein (CaBP) immunocytochemistry at various times after transplantation. At short survival times (5 days after grafting), grafts were confined to the site of the original injection. At longer survival times (7–32 days after grafting), grafted PC formed a migratory stream that reached the cerebellar cortex of the host. The most robust graft development was seen 1 month after grafting, the longest survival time allowed in this series of experiments. At that time, clusters of donor PC were found both in the deep nuclei parenchyma and aligned along cortical folia. The orientation of the dendritic trees of PC that had migrated to the cortex was toward the pia. A CaBP-immunoreactive fibre plexus innervated the host deep cerebellar nuclei. The stream of grafted PC extended from the deep cerebellar nuclei to the cerebellar cortex of the host, indicating that donor PC could establish their axonal contacts in the deep nuclei and then move to their final cortical locality, thus recapitulating a migratory path normally taken during cerebellar ontogeny. It appears therefore that both from the pathophysiological and ontogenetic standpoints, the deep cerebellar nuclei represent the appropriate site for PC implantation in cerebellocortical atrophy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 176 (1987), S. 145-154 
    ISSN: 1432-0568
    Keywords: Neurological mutant mice ; ‘Purkinje cell degeneration’ (pcd) ; Weaver ; Neural transplants ; Cerebellum ; Light microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Embryonic cerebellar grafts from genetically normal donors were implanted into the cerebellomedullary cistern of adult ‘Purkinje cell degeneration’ (pcd) and weaver mutant mice, which are respectively characterized by the selective loss of Purkinje and granule cells. Grafts placed into both mutant recipients exhibited a layered cellular organization reminiscent of the normal cerebellar cortex. Molecular, Purkinje, and granule cell layers were identifiable. Grafted Purkinje cells displayed characteristic cytological features, such as hypolemmal cisterns in association with mitochondria in the perikaryon, and lamellar structures in their axons. The cytological features of granule cell somata in the grafts appeared similar to those of mature granule cells. Electron microscopic examination of the molecular layer of the grafts revealed the presence of parallel fibers, which were not oriented in a parallel fashion; axon terminals of such fibers were often presynaptic to dendritic spines. The number of parallel fibers was markedly reduced in grafts implanted into both mutants compared to the normal cerebellar cortex; however, this phenomenon is commonly seen in cerebellum in tissue culture and in cerebellar transplants into normal hosts. It is concluded, therefore, that the environment of the mutant hosts does not affect the survival of Purkinje or granule cells and that transplantation of solid cerebellar grafts in the neurological mutants studied does not seem to pose any apparent limitations beyond those inherent to the process of cerebellar growth and differentiation outside its normal environment.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 52 (1980), S. 161-164 
    ISSN: 1432-0533
    Keywords: Neurofibrillary degeneration ; Maytansine ; Adult mouse ; Dorsal root ganglion ; Tissue culture ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of maytansine, an antimitotic compound isolated from an African plant, were studied by light and electron microscopy in dissociated cell cultures of adult mouse dorsal root ganglia. Maytansine at 10–100 ng/ml concentration caused reversible, concentration-dependent, inhibition of microtubule assembly and induction of a large amount of 10 nm filaments in the cytoplasm of cultured neurons and Schwann cells.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1106
    Keywords: Heterozygous weaver mice ; Midbrain dopamine neurons ; TH immunochemistry ; Cell count ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The phenotypic effect of theweaver mutation in the ventral midbrain of homozygous mutants is associated with the progressive loss of dopaminergic neurons. To discover whether the number of mesencephalic dopaminergic cells is altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA), and measured cross-sectional areas of neuronal somata in the SN ofwv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in thewv+ ventral midbrain was on average 13% lower than normal. Cell loss was detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles in thewv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses in the SN and VTA correlated with a 13.8% reduction in dopamine level in the ventral striatum inwv/+ mice at 14–16 months of age. Our findings imply that a single dose of theweaver gene in the mouse is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: [3H]Thymidine autoradiography ; Substantia nigra pars compacta ; Retrorubral field ; Ventral tegmental area ; Interfascicular nucleus ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous [3H]thymidine studies in Nisslstained sections in rats established that the substantia nigra pars compacta and the ventral tegmental area originate sequentially according to an anterolateral to posteromedial neurogenetic gradient. We investigated whether that same pattern is found in mice in the dopaminergic neurons in each of these structures. Using tyrosine hydroxylase immunostaining combined with [3H]thymidine autoradiography, the time of origin of dopaminergic midbrain neurons in the retrorubral field, the substantia nigra pars compacta, the ventral tegmental area, and the interfascicular nucleus was determined in postnatal day 20 mice. The dams of the experimental animals were injected with [3H]thymidine on embryonic days (E) 11–E12, E12–E13, E13–E14, and E14–E15. The time of origin profiles for each group indicated significant differences between populations. The retrorubral field and the substantia nigra pars compacta arose nearly simultaneously and contained the highest proportion of neurons, 49 to 37%, generated on or before E11. Progressively fewer early-generated neurons were found in the ventral tegmental area (20%), and the interfascicular nucleus (8.5%). In addition, anterior dorsolateral neurons in the substantia nigra and ventral tegmental area were more likely to be generated early than the posterior ventromedial neurons. These findings indicate that mouse and rat brains have nearly identical developmental patterns in the midbrain, and neurogenetic gradients in dopaminergic neurons are similar to those found in Nissl studies in rats.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: [3H]thymidine autoradiography ; Substantianigra pars compacta ; Retrorubral field, ventral tegmental area ; Interfascicular nucleus ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunocytochemical labeling for tyrosine hydroxylase and [3H]thymidine autoradiography were combined in wild-type mice and in mice homozygous for the weaver mutant gene (wv) to see whether the neurogenetic patterns of midbrain dopaminergic neurons was normal in the mutants and whether the degeneration of dopaminergic neurons was linked to their time of origin. Dams of wild-type and homozygous weaver mice were injected with [3H]thymidine on embryonic days (E) 11–E12, E12–E13, E13–E14, and E14-E15 to label neurons in the retrorubral field, the substantia nigra pars compacta, the ventral tegmental area, and the interfascicular nucleus as they were being generated. The quantitatively determined time of origin profiles indicated that wv/wv mice have the same time span of neurogenesis as +/+ mice (E10 to E14), but have significant deficits in the proportion of late-generated neurons in each dopaminergic population. In the retrorubral field and substantia nigra, weaver homozygotes had substantial losses of dopaminergic neurons and had a greater deficit in the proportion of neurons generated late while, in the ventral tegmental area and interfascicular nucleus, there were slight losses of dopaminergic neurons and only slight deficits in the proportion of late-generated neurons. These findings lead to the conclusion that the weaver gene is specifically targeting dopaminergic neurons that are generated late, mainly on E13 and E14.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1106
    Keywords: Key words Dopamine ; Gene action ; Tissue culture ; Weaver ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The murine weaver (wv) mutation is characterized by a genetically determined loss of several neuronal populations, which include the nigrostriatal dopaminergic neurons. Animals homozygous for the wv gene exhibit marked deficits in dopaminergic morphological and neurochemical parameters. The wv gene shows incomplete dominance in that heterozygous (wv/+) mice exhibit moderate reductions in midbrain dopaminergic neuron number. It is unclear whether the dopaminergic neuronal loss in homozygous and heterozygous animals results from an effect of the wv gene solely on the dopaminergic neurons or is due to a failure of interaction of dopaminergic neurons with target cells of the striatum. This issue has been addressed utilizing three-dimensional reaggregate tissue cultures to determine whether the wv gene acts directly on the mesencephalic dopaminergic neurons. Embryonic mesencephalon and striatum from wv/+ and wild-type (+/+) brains were dissociated and the cells recombined into four mesencephalic-striatal aggregate combinations: (1) mesencephalic(+/+)-striatal(+/+)aggregates; (2) mesencephalic (wv/+) -striatal (wv/+) aggregates; (3) mesencephalic (wv/+) -striatal(+/+)aggregates; and (4) mesencephalic(+/+)-striatal (wv/+) aggregates. At 29 days and 57 days of culture, the number of dopaminergic neurons and dopamine content from mesencephalic-striatal aggregates consisting of mixed genotype or from only wv/+ tissue were quantitated and compared with that from mesencephalic-striatal cultures prepared from +/+ tissue alone. At both culture time points, aggregates containing wv/+ mesencephalon coaggregated with either wv/+ or +/+ striatum contained fewer dopaminergic neurons than mesencephalic-striatal cultures composed of only +/+ cells. Coaggregation of +/+ mesencephalon with wv/+ striatum did not have a detrimental effect on dopaminergic cell number. The findings demonstrate that the difference in the number of mesencephalic dopaminergic neurons between wv/+ and +/+ animals seen in vivo can be reproduced in three-dimensional reaggregate culture. Since the coculture of +/+ striatum with wv/+ mesencephalon did not appear to rescue wv/+ dopaminergic neurons in the aggregates as compared to wv/+ striatum and, wv/+ striatum proved to be a perfectly adequate target for +/+ mesencephalic dopaminergic neurons, it appears that the effect of the wv gene is on the dopaminergic neurons themselves.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 495 (1987), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Two families with Gerstmann-Sträussler-Scheinker disease (GSS) are atypical in possessing neocortical neurofibrillary tangles (NFTs), which are few or absent in other kindreds with GSS, in additon to amyloid plaques that react with prion protein (PrP) antibodies and protease-resistant PrP ...
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] APOLIPOPROTEIN E (APOE) appears to play an important role in the pathogenesis of Alzheimer's disease (AD), as the relative risk of developing late-onset senile dementia of the AD type is increased in individuals who inherit an APOEε4 allele1. In humans, APOE is a single gene located on ...
    Type of Medium: Electronic Resource
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