Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with aging. While deep brain stimulation (DBS) shows therapeutic promise, the long-term persistence of its effects remains understudied. Expression patterns of circulating miRNAs, proposed diagnostic biomarkers,...

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Autores: Riberas Sánchez, Andrea|||0000-0002-1980-5250, García-Brito, Soleil|||0000-0002-4292-3212, Vila Solés, Laia|||0000-0002-7179-9345, Aldavert Vera, Laura|||0000-0002-1506-4790, Segura Torres, Pilar|||0000-0001-6963-8625, Huguet, Gemma|||0000-0002-1439-5053, Carreras-Badosa, Gemma|||0000-0003-2100-0221, Kádár, Elisabet|||0000-0001-9135-4637
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::96742e29c4fde756f1008ec5fb82d94e
Acesso em linha:https://ddd.uab.cat/record/326282
https://dx.doi.org/urn:doi:10.3389/fnagi.2025.1671196
Access Level:acceso abierto
Palavra-chave:Alzheimer's disease
miRNAs
Streptozotocin
Intracranial self-stimulation
Spatial memory
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repository_id_str
spelling Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's diseaseRiberas Sánchez, Andrea|||0000-0002-1980-5250García-Brito, Soleil|||0000-0002-4292-3212Vila Solés, Laia|||0000-0002-7179-9345Aldavert Vera, Laura|||0000-0002-1506-4790Segura Torres, Pilar|||0000-0001-6963-8625Huguet, Gemma|||0000-0002-1439-5053Carreras-Badosa, Gemma|||0000-0003-2100-0221Kádár, Elisabet|||0000-0001-9135-4637Alzheimer's diseasemiRNAsStreptozotocinIntracranial self-stimulationSpatial memoryAlzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with aging. While deep brain stimulation (DBS) shows therapeutic promise, the long-term persistence of its effects remains understudied. Expression patterns of circulating miRNAs, proposed diagnostic biomarkers, and their modulation by DBS are still poorly characterized in longitudinal studies. This study investigates the effect of a 13-week prolonged ICSS treatment on spatial memory and serum miRNA expression in a male rat model of sporadic AD (SAD) by intracerebroventricular injection of streptozotocin (STZ). Morris water maze (MWM) tasks were conducted at 1 and 5 months post-STZ. Serum miRNA levels were quantified by qRT-PCR at 29 (Ser0), 73 (Ser1) and 136 (Ser2) days after STZ administration. Corpus callosum thickness and NRF2 protein levels in the hippocampal CA1 region were assessed using Nissl staining and immunohistochemistry, respectively. Target validation of miR-495 was performed via transfection assays in the human neuroblastoma SH-SY5Y cell line. MFB-ICSS treatment significantly reduced escape latency in the MWM task in the STZ + ICSS group compared to untreated STZ rats at 5 months post-STZ. At Ser0, levels of miR-16, miR-30c, miR-181, miR-191 and miR-196a were significantly increased in STZ group. In STZ rats, miR-146a and miR-495 levels increased from Ser1 to Ser2, an effect not observed in the Control or STZ + ICSS groups. In SH-SY5Y cells, miR-495 overexpression significantly downregulated both NRF2 mRNA and protein levels. Moreover, STZ exposure increased miR-495 and reduced NRF2 protein levels. MFB-ICSS also reversed the STZ-induced reductions in both CA1 NRF2 levels and corpus callosum thickness. Prolonged MFB-ICSS treatment mitigates cognitive deficits, modulates circulating levels of miRNA-495 and miR-146a, restores hippocampal NRF2 levels, and preserves corpus callosum integrity in the SAD rat model by STZ injection. These findings highlight the therapeutic potential of MFB-ICSS as a non-pharmacological intervention in AD. Furthermore, this study confirms NRF2 as a target of miR-495 in the context of AD. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326282https://dx.doi.org/urn:doi:10.3389/fnagi.2025.1671196reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::96742e29c4fde756f1008ec5fb82d94e2026-06-06T12:50:31Z
dc.title.none.fl_str_mv Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
title Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
spellingShingle Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
Riberas Sánchez, Andrea|||0000-0002-1980-5250
Alzheimer's disease
miRNAs
Streptozotocin
Intracranial self-stimulation
Spatial memory
title_short Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
title_full Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
title_fullStr Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
title_full_unstemmed Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
title_sort Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
dc.creator.none.fl_str_mv Riberas Sánchez, Andrea|||0000-0002-1980-5250
García-Brito, Soleil|||0000-0002-4292-3212
Vila Solés, Laia|||0000-0002-7179-9345
Aldavert Vera, Laura|||0000-0002-1506-4790
Segura Torres, Pilar|||0000-0001-6963-8625
Huguet, Gemma|||0000-0002-1439-5053
Carreras-Badosa, Gemma|||0000-0003-2100-0221
Kádár, Elisabet|||0000-0001-9135-4637
author Riberas Sánchez, Andrea|||0000-0002-1980-5250
author_facet Riberas Sánchez, Andrea|||0000-0002-1980-5250
García-Brito, Soleil|||0000-0002-4292-3212
Vila Solés, Laia|||0000-0002-7179-9345
Aldavert Vera, Laura|||0000-0002-1506-4790
Segura Torres, Pilar|||0000-0001-6963-8625
Huguet, Gemma|||0000-0002-1439-5053
Carreras-Badosa, Gemma|||0000-0003-2100-0221
Kádár, Elisabet|||0000-0001-9135-4637
author_role author
author2 García-Brito, Soleil|||0000-0002-4292-3212
Vila Solés, Laia|||0000-0002-7179-9345
Aldavert Vera, Laura|||0000-0002-1506-4790
Segura Torres, Pilar|||0000-0001-6963-8625
Huguet, Gemma|||0000-0002-1439-5053
Carreras-Badosa, Gemma|||0000-0003-2100-0221
Kádár, Elisabet|||0000-0001-9135-4637
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
miRNAs
Streptozotocin
Intracranial self-stimulation
Spatial memory
topic Alzheimer's disease
miRNAs
Streptozotocin
Intracranial self-stimulation
Spatial memory
description Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with aging. While deep brain stimulation (DBS) shows therapeutic promise, the long-term persistence of its effects remains understudied. Expression patterns of circulating miRNAs, proposed diagnostic biomarkers, and their modulation by DBS are still poorly characterized in longitudinal studies. This study investigates the effect of a 13-week prolonged ICSS treatment on spatial memory and serum miRNA expression in a male rat model of sporadic AD (SAD) by intracerebroventricular injection of streptozotocin (STZ). Morris water maze (MWM) tasks were conducted at 1 and 5 months post-STZ. Serum miRNA levels were quantified by qRT-PCR at 29 (Ser0), 73 (Ser1) and 136 (Ser2) days after STZ administration. Corpus callosum thickness and NRF2 protein levels in the hippocampal CA1 region were assessed using Nissl staining and immunohistochemistry, respectively. Target validation of miR-495 was performed via transfection assays in the human neuroblastoma SH-SY5Y cell line. MFB-ICSS treatment significantly reduced escape latency in the MWM task in the STZ + ICSS group compared to untreated STZ rats at 5 months post-STZ. At Ser0, levels of miR-16, miR-30c, miR-181, miR-191 and miR-196a were significantly increased in STZ group. In STZ rats, miR-146a and miR-495 levels increased from Ser1 to Ser2, an effect not observed in the Control or STZ + ICSS groups. In SH-SY5Y cells, miR-495 overexpression significantly downregulated both NRF2 mRNA and protein levels. Moreover, STZ exposure increased miR-495 and reduced NRF2 protein levels. MFB-ICSS also reversed the STZ-induced reductions in both CA1 NRF2 levels and corpus callosum thickness. Prolonged MFB-ICSS treatment mitigates cognitive deficits, modulates circulating levels of miRNA-495 and miR-146a, restores hippocampal NRF2 levels, and preserves corpus callosum integrity in the SAD rat model by STZ injection. These findings highlight the therapeutic potential of MFB-ICSS as a non-pharmacological intervention in AD. Furthermore, this study confirms NRF2 as a target of miR-495 in the context of AD.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv 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://ddd.uab.cat/record/326282
https://dx.doi.org/urn:doi:10.3389/fnagi.2025.1671196
url https://ddd.uab.cat/record/326282
https://dx.doi.org/urn:doi:10.3389/fnagi.2025.1671196
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
https://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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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