Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype

Anxiety and depression are common in Parkinson’s disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity,...

Descripción completa

Detalles Bibliográficos
Autores: Miquel-Rio Luis, Jericó-Escolar, Judith, Sarriés-Serrano, Unai, Yanes-Castilla, Claudia, Torres López, María, Argibay, Uxia, Bortolozzi, Analia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/176789
Acceso en línea:https://hdl.handle.net/11441/176789
https://doi.org/10.1038/s41531-025-01073-1
Access Level:acceso abierto
Palabra clave:Early synaptic
Brain connectivity
id ES_fc4f77a0bdb05f6c24546e44fd3a3fcc
oai_identifier_str oai:idus.us.es:11441/176789
network_acronym_str ES
network_name_str España
repository_id_str
spelling Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotypeMiquel-Rio LuisJericó-Escolar, JudithSarriés-Serrano, UnaiYanes-Castilla, ClaudiaTorres López, MaríaArgibay, UxiaBortolozzi, AnaliaEarly synapticBrain connectivityAnxiety and depression are common in Parkinson’s disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human α-Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with α-Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.Springer Science and Business Media LLCFisiología Médica y BiofísicaEuropean Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Gobierno de EspañaMinisterio de Ciencia e Innovación (MICIN). España2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/176789https://doi.org/10.1038/s41531-025-01073-1reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNpj Parkinson S Disease, 11 (1), 1.PID2022-141700OB-I00https://www.nature.com/articles/s41531-025-01073-1info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1767892026-06-17T12:51:07Z
dc.title.none.fl_str_mv Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
title Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
spellingShingle Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
Miquel-Rio Luis
Early synaptic
Brain connectivity
title_short Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
title_full Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
title_fullStr Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
title_full_unstemmed Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
title_sort Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
dc.creator.none.fl_str_mv Miquel-Rio Luis
Jericó-Escolar, Judith
Sarriés-Serrano, Unai
Yanes-Castilla, Claudia
Torres López, María
Argibay, Uxia
Bortolozzi, Analia
author Miquel-Rio Luis
author_facet Miquel-Rio Luis
Jericó-Escolar, Judith
Sarriés-Serrano, Unai
Yanes-Castilla, Claudia
Torres López, María
Argibay, Uxia
Bortolozzi, Analia
author_role author
author2 Jericó-Escolar, Judith
Sarriés-Serrano, Unai
Yanes-Castilla, Claudia
Torres López, María
Argibay, Uxia
Bortolozzi, Analia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Gobierno de España
Ministerio de Ciencia e Innovación (MICIN). España
dc.subject.none.fl_str_mv Early synaptic
Brain connectivity
topic Early synaptic
Brain connectivity
description Anxiety and depression are common in Parkinson’s disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human α-Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with α-Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/176789
https://doi.org/10.1038/s41531-025-01073-1
url https://hdl.handle.net/11441/176789
https://doi.org/10.1038/s41531-025-01073-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Npj Parkinson S Disease, 11 (1), 1.
PID2022-141700OB-I00
https://www.nature.com/articles/s41531-025-01073-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425410193752064
score 15,812429

Similares en LA Referencia