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  • 1
    Electronic Resource
    Electronic Resource
    Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition (1997)
    [s.l.] : Nature Publishing Group
    Nature genetics 17 (1997), S. 263-264 
    Details
    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
    URL: http://dx.doi.org/10.1038/ng1197-263
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  • 2
    Electronic Resource
    Electronic Resource
    Neurofibrillary tangles in Niemann-Pick disease type C (1995)
    Springer
    Acta neuropathologica 89 (1995), S. 227-238 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuronal storage disease ; Cholesterol ; metabolism ; Tau ; Paired helical filaments ; Lysosomal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course. These were not associated with β-amyloid deposits. The NFT were most frequent in the orbital gyrus, cingulate gyrus and entorhinal region of the cerebral cortex, but were also frequently found in the basal ganglia, thalamus and hypothalamus. In one of the most severely affected case, the NFT were even found in the neurons in the inferior olivary nucleus and in the spinal cord. The NFT were immunostained with Alz 50, and consisted of paired helical filaments. The distribution of the neurons bearing the NFT was generally similar to that of the swollen storage neurons, and storage neurons often contained NFT in their perikarya and/or in the meganeurites. However, neurons with NFT could be noted without swollen perikarya. The coexistence of neuronal storage and NFT in NPC without amyloid deposits suggests that perturbed cholesterol metabolism and/or lysosomal membrane trafficking may play a role in the formation of NFT, and that amyloid deposits are not necessarily the prerequisite for NFT formation. The results of our study also suggest that NFT formation may be a rather nonspecific cellular reaction of neurons to certain slowly progressive metabolic perturbations of an as yet undefined nature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309338
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  • 3
    Electronic Resource
    Electronic Resource
    Neurofibrillary tangles in Niemann-Pick disease type C (1995)
    Springer
    Acta neuropathologica 89 (1995), S. 227-238 
    Details
    ISSN: 1432-0533
    Keywords: Neuronal storage disease ; Cholesterol metabolism ; Tau ; Paired helical filaments ; Lysosomal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course. These were not associated with β-amyloid deposits. The NFT were most frequent in the orbital gyrus, cingulate gyrus and entorhinal region of the cerebral cortex, but were also frequently found in the basal ganglia, thalamus and hypothalamus. In one of the most severely affected case, the NFT were even found in the neurons in the inferior olivary nucleus and in the spinal cord. The NFT were immunostained with Alz 50, and cosisted of paired helical filaments. The distribution of the neurons bearing the NFT was generally similar to that of the swollen storage neurons, and storage neurons often contained NFT in their perikarya and/or in the meganeurites. However, neurons with NFT could be noted without swollen perikarya. The coexistence of neuronal storage and NFT in NPC without amyloid deposits suggests that perturbed cholesterol metabolism and/or lysosomal membrane trafficking may play a role in the formation of NFT, and that amyloid deposits are not necessarily the prerequisite for NFT formation. The results of our study also suggest that NFT formation may be a rather nonspecific cellular reaction of neurons to certain slowly progressive metabolic perturbations of an as yet undefined nature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309338
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  • 4
    Electronic Resource
    Electronic Resource
    In vitro evidence that the reduction in mesencepalic dopaminergic neurons in the weaver heterozygote is not due to a failure in target cell interaction (1997)
    Springer
    Experimental brain research 115 (1997), S. 174-179 
    Details
    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
    URL: http://dx.doi.org/10.1007/PL00005679
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  • 5
    Electronic Resource
    Electronic Resource
    Time of neuron origin and gradients of neurogenesis in midbrain dopaminergic neurons in the mouse (1995)
    Springer
    Experimental brain research 105 (1995), S. 191-199 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00240955
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  • 6
    Electronic Resource
    Electronic Resource
    Systematic differences in time of dopaminergic neuron origin between normal mice and homozygous weaver mutants (1995)
    Springer
    Experimental brain research 105 (1995), S. 200-208 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00240956
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  • 7
    Electronic Resource
    Electronic Resource
    Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice (1997)
    Springer
    Experimental brain research 113 (1997), S. 5-12 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02454137
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  • 8
    Electronic Resource
    Electronic Resource
    Linkage mapping of microdissected clones from distal mouse chromosome 16 (1996)
    Springer
    Somatic cell and molecular genetics 22 (1996), S. 227-232 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A total of 38 unique segments generated by microdissection of mouse chromosome 16 (MMU16), sequence independent amplification (SIA) and cloning were sequentially mapped on the distal portion of the chromosome with two mouse backross panels. Some reference markers from other sources were retyped in the panels and results integrated with those for our microdissected DNA segments. The clone map is most highly refined in its distal portion, which stretches from reference marker D16Mit71 to D16Mit5, and the highest density of clones is in the region defined by markers D16Mit5 and D16Mit141. This map on distal mouse chromosome 16 should be a useful tool for the mouse genome project and for studies of genes in the region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02369912
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