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1000 Titel
  • Inhibition of the Polyamine System Counteracts β-Amyloid Peptide-Induced Memory Impairment in Mice: Involvement of Extrasynaptic NMDA Receptors
1000 Autor/in
  1. Gomes, Guilherme Monteiro |
  2. Dalmolin, Gerusa Duarte |
  3. Bär, Julia |
  4. Karpova, Anna |
  5. Mello, Carlos Fernando |
  6. Kreutz, Michael R. |
  7. Rubin, Maribel Antonello |
1000 Erscheinungsjahr 2014
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2014-06-12
1000 Erschienen in
1000 Quellenangabe
  • 9(6):e99184
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2014
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pone.0099184 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055672/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • In Alzheimer's disease (AD), the β-amyloid peptide (Aβ) has been causally linked to synaptic dysfunction and cognitive impairment. Several studies have shown that N-Methyl-D-Aspartate receptors (NMDAR) activation is involved in the detrimental actions of Aβ. Polyamines, like spermidine and spermine, are positive modulators of NMDAR function and it has been shown that their levels are regulated by Aβ. In this study we show here that interruption of NMDAR modulation by polyamines through blockade of its binding site at NMDAR by arcaine (0.02 nmol/site), or inhibition of polyamine synthesis by DFMO (2.7 nmol/site), reverses Aβ25–35-induced memory impairment in mice in a novel object recognition task. Incubation of hippocampal cell cultures with Aβ25–35 (10 µM) significantly increased the nuclear accumulation of Jacob, which is a hallmark of NMDAR activation. The Aβ-induced nuclear translocation of Jacob was blocked upon application of traxoprodil (4 nM), arcaine (4 µM) or DFMO (5 µM), suggesting that activation of the polyamine binding site at NMDAR located probably at extrasynaptic sites might underlie the cognitive deficits of Aβ25–35-treated mice. Extrasynaptic NMDAR activation in primary neurons results in a stripping of synaptic contacts and simplification of neuronal cytoarchitecture. Aβ25–35 application in hippocampal primary cell cultures reduced dendritic spine density and induced alterations on spine morphology. Application of traxoprodil (4 nM), arcaine (4 µM) or DFMO (5 µM) reversed these effects of Aβ25–35. Taken together these data provide evidence that polyamine modulation of extrasynaptic NMDAR signaling might be involved in Aβ pathology.
1000 Sacherschließung
lokal Neuronal dendrites
lokal Animal behavior
lokal Neurons
lokal Memory
lokal Mice
lokal Object recognition
lokal Alzheimer's disease
lokal Cognitive impairment
1000 Fachgruppe
  1. Biologie |
  2. Medizin |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/R29tZXMsIEd1aWxoZXJtZSBNb250ZWlybw==|https://frl.publisso.de/adhoc/creator/RGFsbW9saW4sIEdlcnVzYSBEdWFydGU=|https://frl.publisso.de/adhoc/creator/QsOkciwgSnVsaWE=|https://frl.publisso.de/adhoc/creator/S2FycG92YSwgQW5uYQ==|https://frl.publisso.de/adhoc/creator/TWVsbG8sIENhcmxvcyBGZXJuYW5kbw==|https://frl.publisso.de/adhoc/creator/S3JldXR6LCBNaWNoYWVsIFIu|https://frl.publisso.de/adhoc/creator/UnViaW4sIE1hcmliZWwgQW50b25lbGxv
1000 Förderer
  1. CNPq |
  2. DAAD |
  3. CAPES |
  4. DFG |
  5. DIP |
  6. German Center for Neurodegenerative Diseases (DZNE) |
  7. Federal state of Saxony-Anhalt |
1000 Fördernummer
  1. 306164/2010-8; 481664/2010-6; 476551/2009-9
  2. -
  3. -
  4. SFB 779 TP B8
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  6. -
  7. -
1000 Förderprogramm
  1. -
  2. -
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  5. -
  6. -
  7. Vorhaben: Center for Behavioral Brain Sciences (CBBS)
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer CNPq |
    1000 Förderprogramm -
    1000 Fördernummer 306164/2010-8; 481664/2010-6; 476551/2009-9
  2. 1000 joinedFunding-child
    1000 Förderer DAAD |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer CAPES |
    1000 Förderprogramm -
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer DFG |
    1000 Förderprogramm -
    1000 Fördernummer SFB 779 TP B8
  5. 1000 joinedFunding-child
    1000 Förderer DIP |
    1000 Förderprogramm -
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer German Center for Neurodegenerative Diseases (DZNE) |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer Federal state of Saxony-Anhalt |
    1000 Förderprogramm Vorhaben: Center for Behavioral Brain Sciences (CBBS)
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6406820.rdf
1000 Erstellt am 2018-02-26T15:53:40.018+0100
1000 Erstellt von 242
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1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Mon May 28 10:06:09 CEST 2018
1000 Objekt bearb. Mon May 28 10:06:08 CEST 2018
1000 Vgl. frl:6406820
1000 Oai Id
  1. oai:frl.publisso.de:frl:6406820 |
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