Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment

Butylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN l...

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Autores: Moyano-Cires Ivanoff, Paula Viviana, Flores, Andrea, Sanjuan, Javier, Plaza Hernández, José Carlos, Guerra Menéndez, Lucía, Abascal, Luisa, Mateo Sierra, Olga, Pino Sans, Javier Del
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/125963
Acesso em linha:https://hdl.handle.net/20.500.14352/125963
Access Level:acceso abierto
Palavra-chave:616.4
AChE
Aβ
HSP70
NRF2 partway
SN56 basal forebrain cholinergic neurons
Tau
Butylparaben
Thyroid hormones
Endocrinología
3205.02 Endocrinología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/125963
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated TreatmentMoyano-Cires Ivanoff, Paula VivianaFlores, AndreaSanjuan, JavierPlaza Hernández, José CarlosGuerra Menéndez, LucíaAbascal, LuisaMateo Sierra, OlgaPino Sans, Javier Del616.4AChEAβHSP70NRF2 partwaySN56 basal forebrain cholinergic neuronsTauButylparabenThyroid hormonesEndocrinología3205.02 EndocrinologíaButylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN loss, we employed BF SN56 cholinergic wild-type or silenced cells for Tau, amyloid-beta precursor protein (βApp), acetylcholinesterase (AChE), or glycogen synthase kinase-3 beta (GSK3β) genes, exposing them to BP (0.1-80 µM) for 1 or 14 days alongside triiodothyronine (T3; 15 nM), N-acetylcysteine (NAC; 1 mM), or recombinant heat shock protein 70 (rHSP70; 30 µM). BP disrupted cholinergic transmission by AChE inhibition and provoked cell death through thyroid hormones (THs) pathway disruption, Aβ/p-Tau protein accumulation, AChE-S overexpression, and oxidative stress (OS). Aβ/p-Tau accumulation was correlated with HSP70 downregulation, OS exacerbation, and GSK3β hyperactivation (for p-Tau). BP-induced OS was mediated by reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (NRF2) pathway disruption. All observed effects were contingent upon TH signaling impairment. These findings uncover novel mechanistic links between BP exposure and BFCN neurodegeneration, providing a framework for therapeutic strategiesMDPIUniversidad Complutense de Madrid20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/125963reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1259632026-06-02T12:44:21Z
dc.title.none.fl_str_mv Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
title Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
spellingShingle Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
Moyano-Cires Ivanoff, Paula Viviana
616.4
AChE
Aβ
HSP70
NRF2 partway
SN56 basal forebrain cholinergic neurons
Tau
Butylparaben
Thyroid hormones
Endocrinología
3205.02 Endocrinología
title_short Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
title_full Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
title_fullStr Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
title_full_unstemmed Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
title_sort Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
dc.creator.none.fl_str_mv Moyano-Cires Ivanoff, Paula Viviana
Flores, Andrea
Sanjuan, Javier
Plaza Hernández, José Carlos
Guerra Menéndez, Lucía
Abascal, Luisa
Mateo Sierra, Olga
Pino Sans, Javier Del
author Moyano-Cires Ivanoff, Paula Viviana
author_facet Moyano-Cires Ivanoff, Paula Viviana
Flores, Andrea
Sanjuan, Javier
Plaza Hernández, José Carlos
Guerra Menéndez, Lucía
Abascal, Luisa
Mateo Sierra, Olga
Pino Sans, Javier Del
author_role author
author2 Flores, Andrea
Sanjuan, Javier
Plaza Hernández, José Carlos
Guerra Menéndez, Lucía
Abascal, Luisa
Mateo Sierra, Olga
Pino Sans, Javier Del
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616.4
AChE
Aβ
HSP70
NRF2 partway
SN56 basal forebrain cholinergic neurons
Tau
Butylparaben
Thyroid hormones
Endocrinología
3205.02 Endocrinología
topic 616.4
AChE
Aβ
HSP70
NRF2 partway
SN56 basal forebrain cholinergic neurons
Tau
Butylparaben
Thyroid hormones
Endocrinología
3205.02 Endocrinología
description Butylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN loss, we employed BF SN56 cholinergic wild-type or silenced cells for Tau, amyloid-beta precursor protein (βApp), acetylcholinesterase (AChE), or glycogen synthase kinase-3 beta (GSK3β) genes, exposing them to BP (0.1-80 µM) for 1 or 14 days alongside triiodothyronine (T3; 15 nM), N-acetylcysteine (NAC; 1 mM), or recombinant heat shock protein 70 (rHSP70; 30 µM). BP disrupted cholinergic transmission by AChE inhibition and provoked cell death through thyroid hormones (THs) pathway disruption, Aβ/p-Tau protein accumulation, AChE-S overexpression, and oxidative stress (OS). Aβ/p-Tau accumulation was correlated with HSP70 downregulation, OS exacerbation, and GSK3β hyperactivation (for p-Tau). BP-induced OS was mediated by reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (NRF2) pathway disruption. All observed effects were contingent upon TH signaling impairment. These findings uncover novel mechanistic links between BP exposure and BFCN neurodegeneration, providing a framework for therapeutic strategies
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/125963
url https://hdl.handle.net/20.500.14352/125963
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425687911202816
score 15.812455

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