TY - JOUR
T1 - Decreased levels of NMDA but not AMPA receptors in the lipid-raft fraction of 3xTg-AD model of Alzheimer's disease
T2 - Relation to Arc/Arg3.1 protein expression
AU - Morin, Jean Pascal
AU - Díaz-Cintra, Sofía
AU - Bermúdez-Rattoni, Federico
AU - Delint-Ramírez, Ilse
N1 - Funding Information:
JPM received a postdoctoral fellowship from the “Programa de Becas de Estancias Posdoctorales”, “Doctorado en Ciencias Biológicas y de la Salud”, Universidad Autónoma Metropolitana (UAM). The authors would like to thank Azucena Aguilar for genotyping, colony management and high-quality technical assistance, Dr. Giovanni Cerón-Solano for help with hippocampus extraction and Dr. Seth Grant, Noboru Komiyama and Maksim Kopanitsa for part of the LTP data presented on Fig. 2 . Special thanks to Dr. Claudia Pérez-Cruz for helpful comments on the manuscript. This work was supported by CONACYT 180919 to IDR, CONACYT 250870 to FB-R, and CONACYT CB2012/178841 and DGAPA, UNAM IN203616 , to SDC.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - It was recently suggested that alteration in lipid raft composition in Alzheimer's disease may lead to perturbations in neurons signalosome, which may help explain the deficits observed in synaptic plasticity mechanisms and long-term memory impairments in AD models. As a first effort to address this issue, we evaluated lipid-raft contents of distinct NMDA and AMPA receptor subunits in the hippocampus of the 3xTg-AD model of Alzheimer's disease. Our results show that compared to controls, 10 months-old 3xTg-AD mice have diminished levels of NMDA receptors in rafts but not in post-synaptic density or total fractions. Additionally, the levels of GluR1 were unaltered in all the analyzed fractions. Finally, we went on to show that the diminished levels of NMDA receptors in rafts correlated with diminished global levels of Arc/Arg3.1, a synaptic protein with a central role in long-term memory formation. This study adds to our current understanding of the signaling pathways disruptions observed in current Alzheimer's disease models.
AB - It was recently suggested that alteration in lipid raft composition in Alzheimer's disease may lead to perturbations in neurons signalosome, which may help explain the deficits observed in synaptic plasticity mechanisms and long-term memory impairments in AD models. As a first effort to address this issue, we evaluated lipid-raft contents of distinct NMDA and AMPA receptor subunits in the hippocampus of the 3xTg-AD model of Alzheimer's disease. Our results show that compared to controls, 10 months-old 3xTg-AD mice have diminished levels of NMDA receptors in rafts but not in post-synaptic density or total fractions. Additionally, the levels of GluR1 were unaltered in all the analyzed fractions. Finally, we went on to show that the diminished levels of NMDA receptors in rafts correlated with diminished global levels of Arc/Arg3.1, a synaptic protein with a central role in long-term memory formation. This study adds to our current understanding of the signaling pathways disruptions observed in current Alzheimer's disease models.
KW - AMPA receptor
KW - Alzheimer
KW - Arc/Arg3.1
KW - Hippocampus
KW - Lipid-raft
KW - NMDA receptor
UR - http://www.scopus.com/inward/record.url?scp=84988826669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988826669&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2016.09.013
DO - 10.1016/j.neuint.2016.09.013
M3 - Article
C2 - 27650435
AN - SCOPUS:84988826669
SN - 0197-0186
VL - 100
SP - 159
EP - 163
JO - Neurochemistry International
JF - Neurochemistry International
ER -