TY - JOUR AU - Varga, Edina AU - Juhász, Gábor AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia AU - Szegedi, Viktor TI - Amyloid-β1-42 disrupts synaptic plasticity by altering glutamate recycling at the synapse JF - JOURNAL OF ALZHEIMER'S DISEASE J2 - J ALZHEIMERS DIS VL - 45 PY - 2015 IS - 2 SP - 449 EP - 456 PG - 8 SN - 1387-2877 DO - 10.3233/JAD-142367 UR - https://m2.mtmt.hu/api/publication/2812783 ID - 2812783 AB - 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. LA - English DB - MTMT ER -