Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease
Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton remodeling. We asked whether alterations in E...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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IOS Press
2010
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| Online Access: | https://hdl.handle.net/10171/13229 |
| _version_ | 1793400051323633664 |
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| author | Simon, A.M. (Ana María) Raquel Ricobaraza, A. (Ana) Escribano, L. (Luis) Schiapparelli, L. (Lucio) Cuadrado-Tejedor, M. (Mar) Perez-Mediavilla, L.A. (Luis Alberto) Avila, J. (Jesús) Rio, J. (Joaquín) del Frechilla, D. (Diana) |
| author_facet | Simon, A.M. (Ana María) Raquel Ricobaraza, A. (Ana) Escribano, L. (Luis) Schiapparelli, L. (Lucio) Cuadrado-Tejedor, M. (Mar) Perez-Mediavilla, L.A. (Luis Alberto) Avila, J. (Jesús) Rio, J. (Joaquín) del Frechilla, D. (Diana) |
| author_sort | Simon, A.M. (Ana María) |
| collection | DSpace |
| description | Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive
decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton
remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model
overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that
EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial
memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels
was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline
in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found
changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may
cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture
increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in
the hippocampus leading to cognitive impairment in a model of AD. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-13229 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2010 |
| publisher | IOS Press |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-132292022-11-28T11:33:57Z Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease Simon, A.M. (Ana María) Raquel Ricobaraza, A. (Ana) Escribano, L. (Luis) Schiapparelli, L. (Lucio) Cuadrado-Tejedor, M. (Mar) Perez-Mediavilla, L.A. (Luis Alberto) Avila, J. (Jesús) Rio, J. (Joaquín) del Frechilla, D. (Diana) Alzheimer's disease Cofilin Ephrin Eph receptor Glutamate receptor LIM-kinase Memory P21-activated kinase Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in the hippocampus leading to cognitive impairment in a model of AD. 2010-10-04T11:40:12Z 2010-10-04T11:40:12Z 2009-01-22 info:eu-repo/semantics/article https://hdl.handle.net/10171/13229 eng info:eu-repo/semantics/openAccess application/pdf IOS Press |
| spellingShingle | Alzheimer's disease Cofilin Ephrin Eph receptor Glutamate receptor LIM-kinase Memory P21-activated kinase Simon, A.M. (Ana María) Raquel Ricobaraza, A. (Ana) Escribano, L. (Luis) Schiapparelli, L. (Lucio) Cuadrado-Tejedor, M. (Mar) Perez-Mediavilla, L.A. (Luis Alberto) Avila, J. (Jesús) Rio, J. (Joaquín) del Frechilla, D. (Diana) Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title | Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title_full | Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title_fullStr | Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title_full_unstemmed | Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title_short | Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease |
| title_sort | early changes in hippocampal eph receptors precede the onset of memory decline in mouse models of alzheimer’s disease |
| topic | Alzheimer's disease Cofilin Ephrin Eph receptor Glutamate receptor LIM-kinase Memory P21-activated kinase |
| url | https://hdl.handle.net/10171/13229 |
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