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  • 1
    Electronic Resource
    Electronic Resource
    Fimbria-Fornix Transections Selectively Down-Regulate Subtypes of Glutamate Transporter and Glutamate Receptor Proteins in Septum and Hippocampus (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 67 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of CNS axotomy on glutamate transporter and glutamate receptor expression were evaluated in adult rats following unilateral fimbria-fornix transections. The septum and hippocampus were collected at 3, 7, 14, and 30 days postlesion. Homogenates were immunoblotted by using antibodies directed against glutamate transporters (GLT-1, GLAST, and EAAC1) and glutamate receptors (GluR1, GluR2/3, GluR6/7, and NMDAR1), and they were assayed for glutamate transport by d-[3H]aspartate binding. GLT-1 was decreased at 7 and 14 days postlesion within the ipsilateral septum and at 7 days postlesion in the hippocampus. GLAST was decreased within the ipsilateral septum and hippocampus at 7 and 14 days postlesion. No postlesion alterations in EAAC1 immunoreactivity were observed. d-[3H]Aspartate binding was decreased at 7, 14, and 30 days postlesion within the ipsilateral septum and 14 days postlesion in the hippocampus. GluR2/3 expression was down-regulated at 30 days postlesion within the ipsilateral septum, whereas GluR1, GluR6/7, and NMDAR1 immunoreactivity was unchanged. In addition, no alterations in glutamate receptor expression were detected within hippocampal homogenates. This study demonstrates a selective down-regulation of primarily glial, and not neuronal, glutamate transporters and a delayed, subtype-specific down-regulation of septal GluR2/3 receptor expression after regional deafferentation within the CNS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.67031208.x
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  • 2
    Electronic Resource
    Electronic Resource
    N-Methyl-d-Aspartate Receptor Proteins NR2A and NR2B Are Differentially Distributed in the Developing Rat Central Nervous System as Revealed by Subunit-Specific Antibodies (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have identified the regional distributions and developmental expression of NMDA-receptor proteins NR2A and NR2B in rat CNS, using two subunit-specific affinity-purified polyclonal antibodies that recognize NR2A and NR2B. In western blots of cells transfected with NR2A or NR2B cDNAs, and of brain homogenates, each antibody detects a single predominant 172-kDa protein corresponding to its homologous subunit. Both subunits are glycoproteins that are enriched in synaptic membranes. In adult rat CNS, NR2A and NR2B are enriched in cortex and hippocampus but are present in other forebrain regions. In hindbrain, NR2A is present at low levels but NR2B is barely detectable. These subunits are differentially expressed in postnatal CNS development. In cortex and striatum, NR2A is absent at birth but expression increases thereafter, whereas NR2B is expressed at nearly adult levels during forebrain development. In hindbrain, low levels of NR2A are present throughout development, whereas NR2B is expressed only transiently in the first postnatal weeks. These results suggest that native NMDA receptors are modulated by NR2A and NR2B in adult forebrain but not appreciably in hindbrain. In contrast, during early postnatal development, NR2B may have a more dominant role than NR2A in modulating NMDA receptors throughout the CNS. Thus, transient changes in NMDA-receptor function may occur during maturation of certain neuronal and/or glial populations via differential expression of NR2A and NR2B subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.66020692.x
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  • 3
    Electronic Resource
    Electronic Resource
    The Copper Chaperone CCS Is Abundant in Neurons and Astrocytes in Human and Rodent Brain (1999)
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 72 (1999), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : Copper trafficking in mammalian cells is highly regulated. CCS is a copper chaperone that donates copper to the antioxidant enzyme copper/zinc superoxide dismutase 1 (SOD 1). Mutations of SOD1 are responsible for ~20% of familial amyotrophic lateral sclerosis (FALS). Monospecific antibodies were generated to evaluate the localization and cellular distribution of this copper chaperone in human and mouse brain as well as other organs. CCS is found to be ubiquitously expressed by multiple tissues and is present in particularly high concentrations in kidney and liver. In brain and spinal cord, CCS was found throughout the neuropil, with expression largely confined to neurons and some astrocytes. Like SOD1, CCS immunoreactivity was intense in Purkinje cells, deep cerebellar neurons, and pyramidal cortical neurons, whereas in spinal cord, CCS was highly expressed in motor neurons. In cortical neurons, CCS was present in the soma and proximal dendrites, as well as some axons. Although the distribution of CCS paralleled that of SOD1, there was a 12-30-fold molar excess of SOD1 over CCS. That both SOD1 and CCS are present, together, in cells that degenerate in ALS also emphasizes the potential role of CCS in mutant SOD1-mediated toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1999.0720422.x
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  • 4
    Electronic Resource
    Electronic Resource
    ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models (1998)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 32 (1998), S. 461-493 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Recent advances in a variety of areas of research, particularly in genetics and in transgenic (Tg)/gene targeting approaches, have had a substantial impact on our understanding of Alzheimer's disease (AD) and related disorders. After briefly reviewing the progress that has been made in diagnostic assessments of patients with senile dementia and in investigations of the neuropathology of AD, we discuss some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E. In addition, we comment on several potential new candidate loci/genes. Subsequently, we review selected recent reports of analyses of a variety of lines of Tg mice that show several neuropathological features of AD, including Abeta-amyloid deposits and dystrophic neurites. Finally, we discuss the several important issues in future investigations of Tg mice, with particular emphasis on the influences of genetic strains on phenotype, especially behavior, and strategies for making new models of neurodegenerative disorders. We believe that investigations of these Tg models will (a) enhance understanding of the relationships between impaired performance on memory tasks and the pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic mechanisms in vivo, (c) lead to identification of new therapeutic targets, and (d) allow testing of new treatment strategies first in mice and then, if successful, in humans with AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.32.1.461
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  • 5
    Electronic Resource
    Electronic Resource
    MUTANT GENES IN FAMILIAL ALZHEIMER'S DISEASE AND TRANSGENIC MODELS (1998)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 21 (1998), S. 479-505 
    Details
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The most common cause of dementia occurring in mid- to late-life is Alzheimer's disease (AD). Some cases of AD, particularly those of early onset, are familial and inherited as autosomal dominant disorders linked to the presence of mutant genes that encode the amyloid precursor protein (APP) or the presenilins (PS1 or PS2). These mutant gene products cause dysfunction/death of vulnerable populations of nerve cells important in memory, higher cognitive processes, and behavior. AD affects 7-10% of individuals 〉65 years of age and perhaps 40% of individuals 〉80 years of age. For the late-onset cases, the principal risk factors are age and apolipoprotein (apoE) allele type, with apoE4 allele being a susceptibility factor. In this review, we briefly discuss the clinical syndrome of AD and the neurobiology/neuropathology of the disease and then focus attention on mutant genes linked to autosomal dominant familial AD (FAD), the biology of the proteins encoded by these genes, and the recent exciting progress in investigations of genetically engineered animal models that express these mutant genes and develop some features of AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.neuro.21.1.479
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  • 6
    Electronic Resource
    Electronic Resource
    Unpleasant pain evoked by thalamic stimulation (1995)
    [s.l.] : Nature Publishing Group
    Nature medicine 1 (1995), S. 885-887 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Classical medical textbook versions of ascending central pathways for pain teach that the spinothalamic system can be functionally subdivided into two components1–3: (1) a lateral ascending projection to the ventroposterior lateral nucleus of the thalamus and hence to somato-sensory cortex, ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0995-885
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  • 7
    Electronic Resource
    Electronic Resource
    Hyperaccumulation of FAD-linked presenilin 1 variants in vivo (1997)
    [s.l.] : Nature Publishing Group
    Nature medicine 3 (1997), S. 756-760 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes can cause Alzheimer's disease in affected members of the majority of early-onset familial Alzheimer's disease (FAD) pedigrees1–7. PS1 encodes an ubiquitously expressed, eight transmembrane protein1,8–11. PS1 is ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0797-756
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  • 8
    Electronic Resource
    Electronic Resource
    New order from neurological disorders (1999)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 399.1999, 6738, A3-, (3 S.) 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The neurological diseases described in this review supplement impact across a wide spectrum of the population. Here, their similarities and differences are highlighted, and common themes of the interactions between basic and clinical sciences for their understanding and treatment are ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/399a003
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  • 9
    Electronic Resource
    Electronic Resource
    Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm (1997)
    [s.l.] : Nature Publishing Group
    Nature 387 (1997), S. 288-292 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In the PS1 targeting construct, an -1.9 kilobase fragment containing the second coding exon (exon 4, amino acids 30-113) and flanking intronic segments of the PS1 gene was replaced by a neomycin-resistance gene (Fig. la). The linearized targeting vector was electroporated into AB2.1 embryonic stem ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/387288a0
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  • 10
    Electronic Resource
    Electronic Resource
    Behavioral reproductive isolation inDrosophila silvestris, D. heteroneura, and their F1 hybrids (Diptera: Drosophilidae) (1995)
    Springer
    Journal of insect behavior 8 (1995), S. 595-616 
    Details
    ISSN: 1572-8889
    Keywords: aggression ; behavior ; courtship ; HawaiianDrosophila ; picture-winged flies ; reproductive isolation ; speciation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We investigated the role that courtship and aggressive interactions may have for the maintenance of reproductive isolation betweenDrosophila silvestris andD. heteroneura. We examined the behavioral bases of reproductive isolation between the parental species and we examined the courtship success of each sex of both reciprocal F1 hybrids when paired with the parental species. We found reduced copulation success among heterotypic parental pairs compared to homotypic pairs, which was primarily due to the lack of courtship initiation betweenD. silvestris males andD. heteroneura females. When hybrid males from both reciprocal crosses were paired with parental females their copulation successes were not significantly different from that of parental males. In contrast, hybrid females from both crosses had reduced copulation success withD. silvestris males, which in turn was primarily due to a reduced success of reaching later stages of courtship. The time spent in copulation by hybrid males was intermediate between the two parental males. We studied aggression by observing the interactions of males of heterotypic pairs, both between the parental species and between the hybrids and parental males. A lack of aggressive interactions betweenD. silvestris males andD. heteroneura males in addition to the lack of courtship suggests thatD. silvestris males do not respond toD. heteroneura individuals of either sex. Hybrid males were equally successful in winning fights with bothD. silvestris andD. heteroneura males. These results indicate that the behavioral isolation betweenD. silvestris andD. heteroneura may be largely a consequence of the earliest stages of interactions. The two species may differ either in activity levels or in morphological or chemical traits that are important for species and mate recognition. The relatively high copulation and aggressive success of hybrids indicates that sexual selection against hybrids alone is unlikely to be a sufficient force to reduce gene flow and maintain species distinctions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01997233
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