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  • 1
    ISSN: 1432-1106
    Keywords: Synapsin I, II ; In situ hybridization ; Northern blot ; Gene expression ; Postnatal brain development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synapsin Ia, Ib, IIa, and IIb are neuronal phosphoproteins, which are supposed to play a role in the short-term regulation of neurotransmitter release. Besides a high degree of homology among the four synapsin subtypes, there are structural differences in the 3′end of their coding region. Here we present the first extensive study of the expression of their gene transcripts by using in situ hybridization and northern blot analysis. Our results show regionally and temporally distinct expression patterns of synapsin Ia, Ib, IIa, and IIb, which suggests different functional properties of the four synapsin subtypes. There was no specific messenger RNA (mRNA) expression of synapsin IIb in most brain regions apart from the cerebellum, suggesting a minor functional role of this synapsin subtype. Synapsin Ia, Ib, and IIa mRNA were expressed earlier in ontogenetically older brain regions such as the piriform cortex, the thalamus, and the hippocampus and later in ontogenetically younger areas such as the neocortex and the cerebellum. Owing to the distinct expression pattern of the synapsin subtypes, we suppose that the synapsins might be essential for the underlying molecular mechanism of pattern formation and plasticity in distinct brain regions during different states of rat brain development.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The normal cellular form of prion protein (PrPC) is a precursor to the pathogenic protease-resistant forms (PrPSc) believed to cause scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt–Jakob disease. Its amino terminus contains the octapeptide ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 87 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrPC and N- and C-terminal fragments of PrPC on the whole-cell current amplitude through voltage-gated calcium channels (VGCCs) of cultured wild-type cerebellar granule cells. With the application of full-length recombinant PrPC (50–500 nm), a highly significant reduction of the whole-cell current amplitude was observed in a dose-dependent manner. Amplitude reduction was abolished when cells were pre-incubated with nifedipine, a specific blocker of voltage-gated L-type calcium channels. N-terminal PrP fragments also led to a dose-dependent reduction of the maximal current amplitude, whereas a C-terminal fragment did not affect the current amplitude. These data demonstrate that nanomolar concentrations of PrPC modulate L-type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper-binding amino-terminal domain of PrPC.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The fundamental physiological function of native cellular prion (PrPC) remains unknown. Herein, the most salient observations as regards prion physiology are critically evaluated. These include: (i) the role of PrPC in copper homeostasis, particularly at the pre-synaptic membrane; (ii) involvement of PrPC in neuronal calcium disturbances; and (iii) the neuroprotective properties of PrPC in response to copper and oxidative stress. Ultimately, a tentative hypothesis of basic prion function is derived, namely that PrPC acts as a sensor for copper and/or free radical stimuli, thereby triggering intracellular calcium signals that finally translate into modulation of synaptic transmission and maintenance of neuronal integrity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previous studies have indicated that recombinant cellular prion protein (PrPC), as well as a synthetic peptide of PrPC, affects intracellular calcium homeostasis. To analyze whether calcium homeostasis in neurons is also affected by a loss of PrPC, we performed microfluorometric calcium measurements on cultured cerebellar granule cells derived from prion protein-deficient (Prnp0/0) mice. The resting concentration of intracellular free calcium ([Ca2+]i) was found to be slightly, but significantly, reduced in Prnp0/0 mouse granule cell neurites. Moreover, we observed a highly significant reduction in the [Ca2+]i increase after high potassium depolarization. Pharmacological studies further revealed that the L-type specific blocker nifedipine, which reduces the depolarization-induced [Ca2+]i increase by 66% in wild-type granule cell somas, has no effect on [Ca2+]i in Prnp0/0 mouse granule cells. Patch-clamp measurements, however, did not reveal a reduced calcium influx through voltage-gated calcium channels in Prnp0/0 mice. These data clearly indicate that loss of PrPC alters the intracellular calcium homeostasis of cultured cerebellar granule cells. There is no evidence, though, that this change is due to a direct alteration of voltage-gated calcium channels.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 7 (1995), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prion protein (PrP) plays a pivotal role in transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. Previous experiments have suggested that the normal cellular prion protein (PrPC) is involved in synaptic function in the hippocampus. Here, we utilized the controlled recording conditions of the patch-clamp technique to investigate the synaptic function of prion protein in cerebellar Purkinje cells. By performing whole-cell and outside-out patch-clamp experiments in thin slices, we investigated synaptic transmission in prion protein knockout mice (PrP-null) and control animals. In PrP-null mice, the kinetics of GABA- and glutamate receptor-mediated currents showed no significant deviation from those in control animals. In contrast to previous results in hippocampal neurons, our findings support the view that synaptic transmission is unimpaired in prion protein-deficient mice.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 9 (1997), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alzheimer's disease and prion diseases such as Creutzfeldt-Jakob disease are caused by as yet undefined metabolic disturbances of normal cellular proteins, the amyloid precursor protein and the prion protein (PrP). Synthetic fragments of both proteins, β-amyloid 25–35 (βA25–35) and PrP106–126, have been shown to be toxic to neurons in culture. Cell death in both cases occurs by apoptosis. Here we show that there are considerable differences in the mechanisms involved. Thus, PrP106–126 is not toxic to cortical cell cultures of PrP knockout mouse neurons whereas PA25–35 is. The toxicity of both peptides involves Ca2+ uptake through voltage-sensitive Ca2+ channels but only PrP106–126 toxicity involves the activity of NMDA receptors. The toxicity of PA25–35, but not PrP106–126, is attenuated by the action of forskolin. These results indicate that PrP106–126 and βA25–35 induce neuronal apoptosis through different mechanisms.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1106
    Keywords: Synapsin I ; In situ hybridization Northern blot ; Gene expression Postnatal brain development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synapsin I is a synaptic phosphoprotein that is involved in the short-term regulation of neurotransmitter release. In this report we present the first extensive study of the developmental expression of its corresponding messenger ribonucleic acid (mRNA) by in situ hybridization and northern blot analysis in rat brain. Synapsin I mRNA showed pronounced differences in expression in different brain regions during postnatal development. The early expression of synapsin I mRNA in ontogenetically older regions such as the thalamus, the piriform cortex and the hippocampus coincides with the earlier maturation of these regions, in contrast to its later expression in ontogenetically younger areas such as the cerebellum and the neocortex. An intriguing expression pattern was found in the hippocampus. In all hippocampal subregions synapsin I mRNA expression increased from postnatal day (PND) 1 to 17. After PND 17, however, there was a marked dissociation between persisting high expression levels in CA3 and the dentate gyrus and a strong decline in synapsin I mRNA expression in CA1. The persistence of synapsin I in some adult rat brain regions indicates that it plays a part in synapse formation during plastic adaption in neuronal connectivities.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Medullomyoblastoma ; Medulloblastoma ; c-myc ; c-erb-B2 ; Allelic loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medullomyoblastoma is a rare variant of medulloblastoma containing myoblastic elements. A 9-year-old boy developed a cerebellar syndrome and signs of increased intracranial pressure, the cause of which was a tumor of the cerebellar vermis measuring 7 × 4.5 × 4.5 cm. Morphologically the tumor largely consisted of a medulloblastoma component but displayed glial, myoblastic and ganglionic differentiation on light microscopic, immunohistochemical and ultrastructural examination. The non-enhancing rim of the tumor on magnetic resonance imaging showed extensive ganglionic differentiation. The tumor did not express bcl-2, c-myc, or c-erb-B2 oncoproteins and was negative for the p53 gene product. On molecular genetic studies, the tumor did not show allelic loss on chromosome loci, frequently altered in medulloblastomas, such as 17p, 1q and 9q.
    Type of Medium: Electronic Resource
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