Please use this identifier to cite or link to this item:
Title: Alteration in the Synaptic and Extrasynaptic Organization of AMPA Receptors in the Hippocampus of P301S Tau Transgenic Mice
Author: Alfaro Ruiz, Rocío
Aguado, Carolina
Martín Belmonte, Alejandro
Moreno Martínez, Ana Esther
Merchán Rubira, Jesús
Hernández, Félix
Ávila, Jesús
Fukazawa, Yugo
Luján, Rafael
Keywords: Malaltia d'Alzheimer
Hipocamp (Cervell)
Alzheimer's disease
Hippocampus (Brain)
Issue Date: 4-Nov-2022
Publisher: MDPI AG
Abstract: Tau pathology is a hallmark of Alzheimer's disease (AD) and other tauopathies, but how pathological tau accumulation alters the glutamate receptor dynamics driving synaptic dysfunction is unclear. Here, we determined the impact of tau pathology on AMPAR expression, density, and subcellular distribution in the hippocampus of P301S mice using immunoblot, histoblot, and quantitative SDS-digested freeze-fracture replica labeling (SDS-FRL). Histoblot and immunoblot showed differential regulation of GluA1 and GluA2 in the hippocampus of P301S mice. The GluA2 subunit was downregulated in the hippocampus at 3 months while both GluA1 and GluA2 subunits were downregulated at 10 months. However, the total amount of GluA1-4 was similar in P301S mice and in age-matched wild-type mice. Using quantitative SDS-FRL, we unraveled the molecular organization of GluA1-4 in various synaptic connections at a high spatial resolution on pyramidal cell spines and interneuron dendrites in the CA1 field of the hippocampus in 10-month-old P301S mice. The labeling density for GluA1-4 in the excitatory synapses established on spines was significantly reduced in P301S mice, compared to age-matched wild-type mice, in the strata radiatum and lacunosum-moleculare but unaltered in the stratum oriens. The density of synaptic GluA1-4 established on interneuron dendrites was significantly reduced in P301S mice in the three strata. The labeling density for GluA1-4 at extrasynaptic sites was significantly reduced in several postsynaptic compartments of CA1 pyramidal cells and interneurons in the three dendritic layers in P301S mice. Our data demonstrate that the progressive accumulation of phospho-tau is associated with alteration of AMPARs on the surface of different neuron types, including synaptic and extrasynaptic membranes, leading to a decline in the trafficking and synaptic transmission, thereby likely contributing to the pathological events taking place in AD.
Note: Reproducció del document publicat a:
It is part of: International Journal of Molecular Sciences, 2022, vol. 23, issue. 21, p. 13527
Related resource:
ISSN: 1422-0067
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
ijms-23-13527.pdf3.58 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons