Amyloid-beta1-42 Disrupts Synaptic Plasticity by Altering Glutamate Recycling at the Synapse

Varga, E [Varga, Edina (Idegtudomány), szerző] Orvosi Vegytani Intézet (SZTE / ÁOK); Juhasz, G [Juhász, Gábor (elektofiziológia), szerző]; Bozso, Z [Bozsó, Zsolt (Peptid kémia), szerző] Orvosi Vegytani Intézet (SZTE / ÁOK); Penke, B [Penke, Botond (Neurodegeneráció,...), szerző] Orvosi Vegytani Intézet (SZTE / ÁOK); Fulop, L [Fülöp, Lívia (Neurodegeneratív ...), szerző] Orvosi Vegytani Intézet (SZTE / ÁOK); Szegedi, V ✉ [Szegedi, Viktor (Idegtudomány), szerző] Biokémiai Intézet (MTA SZBK)

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
Megjelent: JOURNAL OF ALZHEIMER'S DISEASE 1387-2877 1875-8908 45 (2) pp. 449-456 2015
  • SJR Scopus - Clinical Psychology: D1
Azonosítók
Szakterületek:
    Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-beta peptide (Abeta) and neurofibrillary tangles. Evidence has been reported that Abeta1-42 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, Abeta1-42 oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. Abeta 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 Abeta1-42-induced LTP deficit in the CA1. We found that Abeta-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 Abeta induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against Abeta-induced synaptic disruption.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2020-09-28 02:25