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DC Field | Value | Language |
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dc.contributor.author | Hüls, Sandra | - |
dc.contributor.author | Högen, Tobias | - |
dc.contributor.author | Vassallo, Neville | - |
dc.contributor.author | Danzer, Karin M. | - |
dc.contributor.author | Hengerer, Bastian | - |
dc.contributor.author | Giese, Armin | - |
dc.contributor.author | Herms, Jochen | - |
dc.date.accessioned | 2019-08-13T08:28:30Z | - |
dc.date.available | 2019-08-13T08:28:30Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Hüls, S., Högen, T., Vassallo, N., Danzer, K. M., Hengerer, B., Giese, A., & Herms, J. (2011). AMPA‐receptor‐mediated excitatory synaptic transmission is enhanced by iron‐induced α‐synuclein oligomers. Journal of Neurochemistry, 117(5), 868-878. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/45512 | - |
dc.description.abstract | Aggregated α-synuclein (α-syn) is a characteristic pathological finding in Parkinson's disease and related disorders, such as dementia with Lewy bodies. Recent evidence suggests that α-syn oligomers represent the principal neurotoxic species; however, the pathophysiological mechanisms are still not well understood. Here, we studied the neurophysiological effects of various biophysically-characterized preparations of α-syn aggregates on excitatory synaptic transmission in autaptic neuronal cultures. Nanomolar concentrations of large α-syn oligomers, generated by incubation with organic solvent and Fe 3+ ions, were found to selectivity enhance evoked α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor, but not NMDA-receptor, mediated synaptic transmission within minutes. Moreover, the analysis of spontaneous AMPA-receptor-mediated miniature synaptic currents revealed an augmented frequency. These results collectively indicate that large α-syn oligomers alter both pre- and post-synaptic mechanisms of AMPA-receptor-mediated synaptic transmission. The augmented excitatory synaptic transmission may directly contribute to nerve cell death in synucleinopathies. Indeed, already low micromolar glutamate concentrations were found to be toxic in primary cultured neurons incubated with large α-syn oligomers. In conclusion, large α-syn oligomers enhance both pre- and post-synaptic AMPA-receptor-mediated synaptic transmission, thereby aggravating intracellular calcium dyshomeostasis and contributing to excitotoxic nerve cell death in synucleinopathies. | en_GB |
dc.description.sponsorship | This work was supported by the DFG (SFB 596) as well as the German Federal Ministry of Education and Research (Boundesministerium fur Bildung und Forschung), 01EW1006, ImageNinND to J.H.; Research Grant (R09-31-309) from the University of Malta to N.V. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Wiley Online Library | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Receptors, AMPA | en_GB |
dc.subject | Alpha-synuclein | en_GB |
dc.subject | Neural transmission | en_GB |
dc.subject | Parkinson's disease | en_GB |
dc.title | AMPA‐receptor‐mediated excitatory synaptic transmission is enhanced by iron‐induced α‐synuclein oligomers | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1111/j.1471-4159.2011.07254.x | - |
dc.publication.title | Journal of Neurochemistry | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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AMPA‐receptor‐mediated_excitatory_synaptic_transmission_is_enhanced_by_iron‐induced_α‐synuclein_oligomers_2011.pdf | 602.25 kB | Adobe PDF | View/Open |
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