Neuroprotective properties of memantine in different models of excitotoxicity

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2004
Autor:innen
Volbracht, Christiane
van Beek, Johan
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Neurobiology of Aging. Elsevier. 2004, 25(Suppl 2), pp. S412-S413. ISSN 0197-4580. eISSN 1558-1497. Available under: doi: 10.1016/S0197-4580(04)81352-6
Zusammenfassung

Neuronal dysfunction in Alzheimer's disease (AD) may result, in part, from sustained elevations of glutamate levels and increased sensitivity to glutamate, leading to low-level influx of calcium into neurons, impaired neuronal homeostasis and eventually neurodegeneration. Agents that specifically block the pathological stimulation of glutamate receptors, mainly the N-methyl-D-asparate receptor (NMDA-R) might be anticipated to restore physiological function of neurons and thereby have diseasemodifying effects in AD. Previous attemps to use NMDA-R antagonists to retard the progression of AD have been hindered by the psychotomimetic and cardiovascular effects of these drugs. The tolerability of clinically used uncompetitive NMDA-R antagonist memantine is highly dependent on changes in membrane potential and the drug's fast channel unbloeking kinetics. Memantine blocks sustained NMDA-R activation under pathological conditions and rapidly leaves the NMDA-R channel upon transient physiological activation. Objective: We investigated the neuroprotective properties of memantine in cellular models of different complexity. Methods: Organotypic rat hippocampal slices and murine cerebellar granule cell cultures were exposed to different direct or indirect excitotoxins. Death was measured by counting neurons with condensed nuclei. Results: First, an established model was chosen based on the known pharmacological properties of memantine, in order to find relevant concentrations for cell culture expriments. Memantine protected rat neurons in organotypic hippocampal slices from NMDA-indueed excitotoxicity within micromolar range. Next, we tested memantine within the previously determined dose range in neuronal stress models, which are dependent on excitation of cells by endogenous glutamate. Memantine protected routine cerebellar granule cells from apoptosis induced by the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+). Furthermore, neuronal apoptosis induced by the pathophysiologicai mediator nitric oxide (NO) released from S-nitrosoglutathione (GSNO) was inhibited by memantine. Additionally, memantine prevented apoptosis induced by oxygen-glucose deprivation (OGD), a model of cerebral isehemia, in cerebellar granule cells. Conclusion: These findings support a beneficial effect of NMDA-R inhibition by memantine in different apoptotic models.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690VOLBRACHT, Christiane, Johan VAN BEEK, Marcel LEIST, 2004. Neuroprotective properties of memantine in different models of excitotoxicity. In: Neurobiology of Aging. Elsevier. 2004, 25(Suppl 2), pp. S412-S413. ISSN 0197-4580. eISSN 1558-1497. Available under: doi: 10.1016/S0197-4580(04)81352-6
BibTex
@article{Volbracht2004Neuro-52216,
  year={2004},
  doi={10.1016/S0197-4580(04)81352-6},
  title={Neuroprotective properties of memantine in different models of excitotoxicity},
  number={Suppl 2},
  volume={25},
  issn={0197-4580},
  journal={Neurobiology of Aging},
  pages={S412--S413},
  author={Volbracht, Christiane and van Beek, Johan and Leist, Marcel},
  note={Meeting Abstract}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52216">
    <dc:creator>van Beek, Johan</dc:creator>
    <dc:creator>Volbracht, Christiane</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-12-22T09:18:37Z</dcterms:available>
    <dcterms:abstract xml:lang="eng">Neuronal dysfunction in Alzheimer's disease (AD) may result, in part, from sustained elevations of glutamate levels and increased sensitivity to glutamate, leading to low-level influx of calcium into neurons, impaired neuronal homeostasis and eventually neurodegeneration. Agents that specifically block the pathological stimulation of glutamate receptors, mainly the N-methyl-D-asparate receptor (NMDA-R) might be anticipated to restore physiological function of neurons and thereby have diseasemodifying effects in AD. Previous attemps to use NMDA-R antagonists to retard the progression of AD have been hindered by the psychotomimetic and cardiovascular effects of these drugs. The tolerability of clinically used uncompetitive NMDA-R antagonist memantine is highly dependent on changes in membrane potential and the drug's fast channel unbloeking kinetics. Memantine blocks sustained NMDA-R activation under pathological conditions and rapidly leaves the NMDA-R channel upon transient physiological activation. Objective: We investigated the neuroprotective properties of memantine in cellular models of different complexity. Methods: Organotypic rat hippocampal slices and murine cerebellar granule cell cultures were exposed to different direct or indirect excitotoxins. Death was measured by counting neurons with condensed nuclei. Results: First, an established model was chosen based on the known pharmacological properties of memantine, in order to find relevant concentrations for cell culture expriments. Memantine protected rat neurons in organotypic hippocampal slices from NMDA-indueed excitotoxicity within micromolar range. Next, we tested memantine within the previously determined dose range in neuronal stress models, which are dependent on excitation of cells by endogenous glutamate. Memantine protected routine cerebellar granule cells from apoptosis induced by the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+). Furthermore, neuronal apoptosis induced by the pathophysiologicai mediator nitric oxide (NO) released from S-nitrosoglutathione (GSNO) was inhibited by memantine. Additionally, memantine prevented apoptosis induced by oxygen-glucose deprivation (OGD), a model of cerebral isehemia, in cerebellar granule cells. Conclusion: These findings support a beneficial effect of NMDA-R inhibition by memantine in different apoptotic models.</dcterms:abstract>
    <dcterms:title>Neuroprotective properties of memantine in different models of excitotoxicity</dcterms:title>
    <dcterms:issued>2004</dcterms:issued>
    <dc:language>eng</dc:language>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-12-22T09:18:37Z</dc:date>
    <dc:rights>terms-of-use</dc:rights>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>van Beek, Johan</dc:contributor>
    <dc:contributor>Volbracht, Christiane</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52216"/>
    <dc:creator>Leist, Marcel</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Meeting Abstract
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Nein
Diese Publikation teilen