---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17293'
abstract:
- lang: eng
text: Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating
neurotransmitter release, thus contributing to synaptic plasticity and to processes
such as learning and memory. Despite their recognized importance in neural function,
there is limited information on their potential involvement in neurodegenerative
conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact
of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels
in the hippocampus in association with GABAB receptors. Histoblotting experiments
showed that the density of CaV2.1 channel was significantly reduced in the hippocampus
of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in
the active zone of the axon terminals and was present at a very low density over
the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative
SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the
density of CaV2.1 channel in the active zone was significantly reduced in the
strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum
oriens. The decline in Cav2.1 channel density was found to be associated with
a corresponding impairment in the GABAergic synaptic function, as evidenced by
electrophysiological experiments carried out in the hippocampus of APP/PS1 mice.
Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1
receptor in nanodomains (~40–50 nm) in wild type mice, while in APP/PS1 mice this
nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced
reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a
role in the synaptic transmission alterations shown in the AD hippocampus. Therefore,
uncovering these layer-dependent changes in P/Q calcium currents associated with
AD pathology can benefit the development of future strategies for AD management.
acknowledgement: "Funding sources were Spanish Ministerio de Economía y Competitividad,
Junta de Comunidades de Castilla-La Mancha (Spain), Life Science Innovation Center
at University of Fukui and German Research Foundation.\r\nGrants RTI2018-095812-B-I00
and PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A
way of making Europe” to Rafael Luján. This study was also supported by a grant
from Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064)
and Universidad de Castilla-La Mancha (2023-GRIN-34187) to Rafael Luján, and Life
Science Innovation Center (Research and Education Program for Life Science) at University
of Fukui and JSPS KAKENHI Grant Numbers 16H04662, 17K19446, 18H05120 to Yugo Fukazawa
and Margarita Salas fellowship from Ministerio de Universidades and Universidad
de Castilla-La Mancha to Alejandro Martín-Belmonte. German Research Foundation (DFG
FOR 2143) and BIOSS-2 to Akos Kulik."
article_number: e13279
article_processing_charge: Yes
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: Akos
full_name: Kulik, Akos
last_name: Kulik
- first_name: Luis
full_name: de la Ossa, Luis
last_name: de la Ossa
- first_name: Ana Esther
full_name: Moreno‐Martínez, Ana Esther
last_name: Moreno‐Martínez
- first_name: Samuel
full_name: Alberquilla, Samuel
last_name: Alberquilla
- first_name: Lucía
full_name: García‐Carracedo, Lucía
last_name: García‐Carracedo
- first_name: Miriam
full_name: Fernández, Miriam
last_name: Fernández
- first_name: Ana
full_name: Fajardo‐Serrano, Ana
last_name: Fajardo‐Serrano
- first_name: Ester
full_name: Aso, Ester
last_name: Aso
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Eduardo D.
full_name: Martín, Eduardo D.
last_name: Martín
- 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. Nanoarchitecture of CaV>2.1
channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology.
Brain Pathology. 2025;35(2). doi:10.1111/bpa.13279'
apa: 'Martín‐Belmonte, A., Aguado, C., Alfaro‐Ruiz, R., Kulik, A., de la Ossa, L.,
Moreno‐Martínez, A. E., … Luján, R. (2025). Nanoarchitecture of CaV>2.1 channels
and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. Brain
Pathology. Wiley. https://doi.org/10.1111/bpa.13279'
chicago: 'Martín‐Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro‐Ruiz, Akos Kulik,
Luis de la Ossa, Ana Esther Moreno‐Martínez, Samuel Alberquilla, et al. “Nanoarchitecture
of CaV>2.1 Channels and GABAB Receptors in the Mouse Hippocampus: Impact of
APP/PS1 Pathology.” Brain Pathology. Wiley, 2025. https://doi.org/10.1111/bpa.13279.'
ieee: 'A. Martín‐Belmonte et al., “Nanoarchitecture of CaV>2.1 channels
and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology,” Brain
Pathology, vol. 35, no. 2. Wiley, 2025.'
ista: 'Martín‐Belmonte A, Aguado C, Alfaro‐Ruiz R, Kulik A, de la Ossa L, Moreno‐Martínez
AE, Alberquilla S, García‐Carracedo L, Fernández M, Fajardo‐Serrano A, Aso E,
Shigemoto R, Martín ED, Fukazawa Y, Ciruela F, Luján R. 2025. Nanoarchitecture
of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of
APP/PS1 pathology. Brain Pathology. 35(2), e13279.'
mla: 'Martín‐Belmonte, Alejandro, et al. “Nanoarchitecture of CaV>2.1 Channels
and GABAB Receptors in the Mouse Hippocampus: Impact of APP/PS1 Pathology.” Brain
Pathology, vol. 35, no. 2, e13279, Wiley, 2025, doi:10.1111/bpa.13279.'
short: A. Martín‐Belmonte, C. Aguado, R. Alfaro‐Ruiz, A. Kulik, L. de la Ossa, A.E.
Moreno‐Martínez, S. Alberquilla, L. García‐Carracedo, M. Fernández, A. Fajardo‐Serrano,
E. Aso, R. Shigemoto, E.D. Martín, Y. Fukazawa, F. Ciruela, R. Luján, Brain Pathology
35 (2025).
date_created: 2024-07-22T07:48:20Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2025-05-19T13:58:12Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1111/bpa.13279
external_id:
isi:
- '001250034200001'
pmid:
- '38887180'
file:
- access_level: open_access
checksum: 75a172800ab2e949abb66fba97cf70f0
content_type: application/pdf
creator: dernst
date_created: 2025-04-16T09:56:08Z
date_updated: 2025-04-16T09:56:08Z
file_id: '19582'
file_name: 2025_BrainPathology_MartinBelmonte.pdf
file_size: 8767863
relation: main_file
success: 1
file_date_updated: 2025-04-16T09:56:08Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '2'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Brain Pathology
publication_identifier:
eissn:
- 1750-3639
issn:
- 1015-6305
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus:
Impact of APP/PS1 pathology'
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 35
year: '2025'
...