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  -