Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist

In Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor...

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Autores: Companys Alemany, Júlia, Turcu, Andreea L., Vázquez Cruz, Santiago, Pallàs i Llibería, Mercè, 1964-, Griñán Ferré, Christian
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/194102
Acesso em linha:https://hdl.handle.net/2445/194102
Access Level:acceso abierto
Palavra-chave:Envelliment
Malaltia d'Alzheimer
Receptors cel·lulars
Aging
Alzheimer's disease
Cell receptors
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spelling Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonistCompanys Alemany, JúliaTurcu, Andreea L.Vázquez Cruz, SantiagoPallàs i Llibería, Mercè, 1964-Griñán Ferré, ChristianEnvellimentMalaltia d'AlzheimerReceptors cel·lularsAgingAlzheimer's diseaseCell receptorsIn Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor antagonist, UB-ALT-EV and memantine, as a gold standard, have been evaluated in 5XFAD mice. Following treatment with UB-ALT-EV, nor memantine, changes in the calcineurin (CaN)/NFAT pathway were detected. UB-ALT-EV increased neurotropic factors (Bdnf, Vgf and Ngf) gene expression. Treatments reduced astrocytic and microglial reactivity as revealed by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) quantification. Interestingly, only UB-ALT-EV was able to reduce gene expression of Trem2, a marker of microglial activation and NF-κB. Pro-inflammatory cytokines Il-1β, Ifn-γ, Ccl2 and Ccl3 were down-regulated in UB-ALT-EV-treated mice but not in memantine-treated mice. Interestingly, the anti-inflammatory markers of the M2-migroglial phenotype, chitinase-like 3 (Ym1) and Arginase-1 (Arg1), were up-regulated after treatment with UB-ALT-EV. Since iNOS gene expression decreased after UB-ALT-EV treatment, a qPCR array containing 84 OS-related genes was performed. We found changes in Il-19, Il-22, Gpx6, Ncf1, Aox1 and Vim gene expression after UB-ALT-EV. Hence, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.Nature Publishing Group2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/194102Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-022-22963-xScientific Reports, 2022, vol. 12, p. 17908https://doi.org/10.1038/s41598-022-22963-xcc-by (c) Companys Alemany, Júlia et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1941022026-05-27T06:46:51Z
dc.title.none.fl_str_mv Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
title Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
spellingShingle Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
Companys Alemany, Júlia
Envelliment
Malaltia d'Alzheimer
Receptors cel·lulars
Aging
Alzheimer's disease
Cell receptors
title_short Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
title_full Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
title_fullStr Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
title_full_unstemmed Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
title_sort Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist
dc.creator.none.fl_str_mv Companys Alemany, Júlia
Turcu, Andreea L.
Vázquez Cruz, Santiago
Pallàs i Llibería, Mercè, 1964-
Griñán Ferré, Christian
author Companys Alemany, Júlia
author_facet Companys Alemany, Júlia
Turcu, Andreea L.
Vázquez Cruz, Santiago
Pallàs i Llibería, Mercè, 1964-
Griñán Ferré, Christian
author_role author
author2 Turcu, Andreea L.
Vázquez Cruz, Santiago
Pallàs i Llibería, Mercè, 1964-
Griñán Ferré, Christian
author2_role author
author
author
author
dc.subject.none.fl_str_mv Envelliment
Malaltia d'Alzheimer
Receptors cel·lulars
Aging
Alzheimer's disease
Cell receptors
topic Envelliment
Malaltia d'Alzheimer
Receptors cel·lulars
Aging
Alzheimer's disease
Cell receptors
description In Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor antagonist, UB-ALT-EV and memantine, as a gold standard, have been evaluated in 5XFAD mice. Following treatment with UB-ALT-EV, nor memantine, changes in the calcineurin (CaN)/NFAT pathway were detected. UB-ALT-EV increased neurotropic factors (Bdnf, Vgf and Ngf) gene expression. Treatments reduced astrocytic and microglial reactivity as revealed by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) quantification. Interestingly, only UB-ALT-EV was able to reduce gene expression of Trem2, a marker of microglial activation and NF-κB. Pro-inflammatory cytokines Il-1β, Ifn-γ, Ccl2 and Ccl3 were down-regulated in UB-ALT-EV-treated mice but not in memantine-treated mice. Interestingly, the anti-inflammatory markers of the M2-migroglial phenotype, chitinase-like 3 (Ym1) and Arginase-1 (Arg1), were up-regulated after treatment with UB-ALT-EV. Since iNOS gene expression decreased after UB-ALT-EV treatment, a qPCR array containing 84 OS-related genes was performed. We found changes in Il-19, Il-22, Gpx6, Ncf1, Aox1 and Vim gene expression after UB-ALT-EV. Hence, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.
publishDate 2022
dc.date.none.fl_str_mv 2022
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/2445/194102
url https://hdl.handle.net/2445/194102
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-22963-x
Scientific Reports, 2022, vol. 12, p. 17908
https://doi.org/10.1038/s41598-022-22963-x
dc.rights.none.fl_str_mv cc-by (c) Companys Alemany, Júlia et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Companys Alemany, Júlia et al., 2022
https://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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.223283

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