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Amyloid-?1-42 Disrupts Synaptic Plasticity by Altering Glutamate Recycling at the Synapse.

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Tartalom: http://real.mtak.hu/26619/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
Amyloid-?1-42 Disrupts Synaptic Plasticity by Altering Glutamate Recycling at the Synapse.
Létrehozó:
Varga, Edina
Juhász, Gábor
Bozsó, Zsolt
Penke, Botond
Fülöp, Lívia
Szegedi, Viktor
Dátum:
2015
Téma:
QP Physiology / élettan
RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Tartalmi leírás:
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-? peptide (A?) and neurofibrillary tangles. Evidence has been reported that A?(1-42) plays an essential pathogenic role in decreased spine density, impairment of synaptic plasticity, and neuronal loss with disruption of memory-related synapse function, all associated with AD. Experimentally, A?(1-42) oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. A? was also reported to perturb synaptic glutamate (Glu)-recycling by inhibiting excitatory-amino-acid-transporters. Elevated level of extracellular Glu leads to activation of perisynaptic receptors, including NR2B subunit containing NMDARs. These receptors were shown to induce impaired LTP and enhanced long-term depression and proapoptotic pathways, all central features of AD. In the present study, we investigated the role of Glu-recycling on A?(1-42)-induced LTP deficit in the CA1. We found that A?-induced LTP damage, which was mimicked by the Glu-reuptake inhibitor TBOA, could be rescued by blocking the NR2B subunit of NMDA receptors. Furthermore, decreasing the level of extracellular Glu using a Glu scavenger also restores TBOA or A? induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against A?-induced synaptic disruption.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Varga, Edina and Juhász, Gábor and Bozsó, Zsolt and Penke, Botond and Fülöp, Lívia and Szegedi, Viktor (2015) Amyloid-?1-42 Disrupts Synaptic Plasticity by Altering Glutamate Recycling at the Synapse. Journal of Alzheimer's disease : JAD, 45 (2). pp. 449-56. ISSN 1875-8908
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