Amyloid-β1-42 disrupts synaptic plasticity by altering glutamate recycling at the synapse
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-β peptide (Aβ) and neurofibrillary tangles. Evidence has been reported that Aβ(1-42) plays an essential pathogenic role in decreased spine density, impairment...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2015
|
| Sorozat: | Journal of Alzheimer's disease : JAD
45 No. 2 |
| doi: | 10.3233/JAD-142367 |
| mtmt: | 2812783 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/12351 |
| Tartalmi kivonat: | Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-β peptide (Aβ) and neurofibrillary tangles. Evidence has been reported that Aβ(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, Aβ(1-42) oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. Aβ 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 Aβ(1-42)-induced LTP deficit in the CA1. We found that Aβ-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 Aβ induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against Aβ-induced synaptic disruption. |
|---|---|
| Terjedelem/Fizikai jellemzők: | 449-456 |
| ISSN: | 1875-8908 |