---
_id: '12212'
abstract:
- lang: eng
  text: Alzheimer’s disease (AD) is characterized by a reorganization of brain activity
    determining network hyperexcitability and loss of synaptic plasticity. Precisely,
    a dysfunction in metabotropic GABAB receptor signalling through G protein-gated
    inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated.
    Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density,
    subcellular distribution, and its association with GABAB receptors in hippocampal
    CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested
    freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay
    (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic
    gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in
    spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed
    a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but
    not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed
    a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and
    axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3,
    was significantly reduced along the neuronal surface of CA1 pyramidal cells and
    in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering
    was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant
    reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model.
    Overall, our results provide compelling evidence showing a significant reduction
    on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not
    GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal
    pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the
    GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB
    signalling via GIRK channels in this AD animal model.
acknowledgement: "We thank Ms. Diane Latawiec for the English revision of the manuscript.
  Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta
  de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center
  at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat
  de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako
  Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis
  work was supported by grants from the Spanish Ministerio de Economía y Competitividad
  (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades
  de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL,
  Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers
  16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio
  de Universidades and Universidad de Castilla-La Mancha to AMB."
article_number: '136'
article_processing_charge: No
article_type: original
author:
- first_name: Alejandro
  full_name: Martín-Belmonte, Alejandro
  last_name: Martín-Belmonte
- first_name: Carolina
  full_name: Aguado, Carolina
  last_name: Aguado
- first_name: Rocío
  full_name: Alfaro-Ruiz, Rocío
  last_name: Alfaro-Ruiz
- first_name: Ana Esther
  full_name: Moreno-Martínez, Ana Esther
  last_name: Moreno-Martínez
- first_name: Luis
  full_name: de la Ossa, Luis
  last_name: de la Ossa
- first_name: Ester
  full_name: Aso, Ester
  last_name: Aso
- first_name: Laura
  full_name: Gómez-Acero, Laura
  last_name: Gómez-Acero
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Yugo
  full_name: Fukazawa, Yugo
  last_name: Fukazawa
- first_name: Francisco
  full_name: Ciruela, Francisco
  last_name: Ciruela
- first_name: Rafael
  full_name: Luján, Rafael
  last_name: Luján
citation:
  ama: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in
    GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice.
    <i>Alzheimer’s Research &#38; Therapy</i>. 2022;14. doi:<a href="https://doi.org/10.1186/s13195-022-01078-5">10.1186/s13195-022-01078-5</a>
  apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de
    la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors
    and GIRK channel organization on the hippocampus of APP/PS1 mice. <i>Alzheimer’s
    Research &#38; Therapy</i>. Springer Nature. <a href="https://doi.org/10.1186/s13195-022-01078-5">https://doi.org/10.1186/s13195-022-01078-5</a>
  chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther
    Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale
    Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus
    of APP/PS1 Mice.” <i>Alzheimer’s Research &#38; Therapy</i>. Springer Nature,
    2022. <a href="https://doi.org/10.1186/s13195-022-01078-5">https://doi.org/10.1186/s13195-022-01078-5</a>.
  ieee: A. Martín-Belmonte <i>et al.</i>, “Nanoscale alterations in GABAB receptors
    and GIRK channel organization on the hippocampus of APP/PS1 mice,” <i>Alzheimer’s
    Research &#38; Therapy</i>, vol. 14. Springer Nature, 2022.
  ista: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa
    L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale
    alterations in GABAB receptors and GIRK channel organization on the hippocampus
    of APP/PS1 mice. Alzheimer’s Research &#38; Therapy. 14, 136.
  mla: Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors
    and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” <i>Alzheimer’s
    Research &#38; Therapy</i>, vol. 14, 136, Springer Nature, 2022, doi:<a href="https://doi.org/10.1186/s13195-022-01078-5">10.1186/s13195-022-01078-5</a>.
  short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de
    la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján,
    Alzheimer’s Research &#38; Therapy 14 (2022).
date_created: 2023-01-16T09:45:51Z
date_published: 2022-09-21T00:00:00Z
date_updated: 2023-08-04T09:23:10Z
day: '21'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1186/s13195-022-01078-5
external_id:
  isi:
  - '000857985500001'
file:
- access_level: open_access
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  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-27T07:53:18Z
  date_updated: 2023-01-27T07:53:18Z
  file_id: '12413'
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  relation: main_file
  success: 1
file_date_updated: 2023-01-27T07:53:18Z
has_accepted_license: '1'
intvolume: '        14'
isi: 1
keyword:
- Cognitive Neuroscience
- Neurology (clinical)
- Neurology
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Alzheimer's Research & Therapy
publication_identifier:
  issn:
  - 1758-9193
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nanoscale alterations in GABAB receptors and GIRK channel organization on the
  hippocampus of APP/PS1 mice
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 14
year: '2022'
...