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dc.contributor.author | Sánchez Rodríguez, Irene | |
dc.contributor.author | Djebari, Souhail | |
dc.contributor.author | Temprano Carazo, Sara | |
dc.contributor.author | Vega Avelaira, David | |
dc.contributor.author | Jiménez Herrera, Raquel | |
dc.contributor.author | Iborra Lázaro, Guillermo | |
dc.contributor.author | Yajeya, Javier | |
dc.contributor.author | JIménez Díaz, Lidia | |
dc.contributor.author | Navarro López, Juan D. | |
dc.date.accessioned | 2021-11-08T11:02:18Z | |
dc.date.available | 2021-11-08T11:02:18Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Sánchez-Rodríguez, I., Djebari, S., Temprano-Carazo, S., Vega-Avelaira, D., Jiménez-Herrera, R., Iborra-Lázaro, G., Yajeya, J., Jiménez-Díaz, L., & Navarro-López, J. D. (2020). Hippocampal long-term synaptic depression and memory deficits induced in early amyloidopathy are prevented by enhancing G-protein-gated inwardly rectifying potassium channel activity. Journal of Neurochemistry, 153(3), 362–376. https://doi.org/10.1111/jnc.14946 | spa |
dc.identifier.issn | 0022-3042 | |
dc.identifier.issn | 1471-4159 | |
dc.identifier.uri | http://hdl.handle.net/11268/10482 | |
dc.description.abstract | Hippocampal synaptic plasticity disruption by amyloid-β (Aβ) peptides + thought to be responsible for learning and memory impairments in Alzheimer's disease (AD) early stage. Failures in neuronal excitability maintenance seems to be an underlying mechanism. G-protein-gated inwardly rectifying potassium (GirK) channels control neural excitability by hyperpolarization in response to many G-protein-coupled receptors activation. Here, in early in vitro and in vivo amyloidosis mouse models, we study whether GirK channels take part of the hippocampal synaptic plasticity impairments generated by Aβ1-42 . In vitro electrophysiological recordings from slices showed that Aβ1-42 alters synaptic plasticity by switching high-frequency stimulation (HFS) induced long-term potentiation (LTP) to long-term depression (LTD), which led to in vivo hippocampal-dependent memory deficits. Remarkably, selective pharmacological activation of GirK channels with ML297 rescued both HFS-induced LTP and habituation memory from Aβ1-42 action. Moreover, when GirK channels were specifically blocked by Tertiapin-Q, their activation with ML297 failed to rescue LTP from the HFS-dependent LTD induced by Aβ1-42 . On the other hand, the molecular analysis of the recorded slices by western blot showed that the expression of GIRK1/2 subunits, which form the prototypical GirK channel in the hippocampus, was not significantly regulated by Aβ1-42 . However, immunohistochemical examination of our in vivo amyloidosis model showed Aβ1-42 to down-regulate hippocampal GIRK1 subunit expression. Together, our results describe an Aβ-mediated deleterious synaptic mechanism that modifies the induction threshold for hippocampal LTP/LTD and underlies memory alterations observed in amyloidosis models. In this scenario, GirK activation assures memory formation by preventing the transformation of HFS-induced LTP into LTD. | spa |
dc.description.sponsorship | Spanish Ministry of Economy and Competitivity MINECO-FEDER, Grant (BFU2014-56164-P and BFU2017-82494-P) | spa |
dc.description.sponsorship | Fundación Tatiana Pérez de Guzmán el Bueno | spa |
dc.description.sponsorship | University of Castilla la Mancha | spa |
dc.language.iso | eng | spa |
dc.subject.other | Depresión | spa |
dc.subject.other | Neuroquímica | spa |
dc.subject.other | Memoria | spa |
dc.title | Hippocampal long-term synaptic depression and memory deficits induced in early amyloidopathy are prevented by enhancing G-protein-gated inwardly-rectifying potassium channel activity | spa |
dc.type | article | spa |
dc.description.impact | 5.372 JCR (2020) Q1, 78/295 Biochemistry & Molecular Biology | spa |
dc.description.impact | 1.75 SJR (2020) Q1, 69/438 Biochemistry | spa |
dc.description.impact | No data IDR 2020 | spa |
dc.identifier.doi | 10.1111/jnc.14946 | |
dc.rights.accessRights | openAccess | spa |
dc.subject.unesco | Investigación sobre el cerebro | spa |
dc.description.filiation | UEM | spa |
dc.relation.publisherversion | https://doi.org/10.1111/jnc.15536 | eng |
dc.peerreviewed | Si | spa |
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