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Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease
Authors: Simon, A.M. (Ana María)
Lopez-de-Maturana, R. (Raquel)
Ricobaraza, A. (Ana)
Escribano, L. (L.)
Schiapparelli, L. (Lucio)
Cuadrado-Tejedor, M. (Mar)
Perez-Mediavilla, L.A. (Luis Alberto)
Avila, J. (Jesús)
Rio, J. (Joaquín) del
Frechilla, D. (Diana)
Keywords: Alzheimer's disease
Cofilin
Ephrin
Eph receptor
Glutamate receptor
LIM-kinase
Memory
P21-activated kinase
Issue Date: 22-Jan-2009
Publisher: IOS Press
Publisher version: http://dx.doi.org/10.3233/JAD-2009-1096
ISBN: 1387-2877
Citation: Simon AM, de Maturana RL, Ricobaraza A, Escribano L, Schiapparelli L, Cuadrado-Tejedor M, et al. Early changes in hippocampal Eph receptors precede the onset of memory decline in mouse models of Alzheimer's disease. J Alzheimers Dis 2009;17(4):773-786.
Abstract
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.
Permanent link: http://hdl.handle.net/10171/13229
Appears in Collections:DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista
DA - Medicina - Anatomía - Artículos de revista
DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista

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