GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model

Autores
Vidal Escobedo, Ana Abril; Peralta, Facundo; Morel, Gustavo Ramón; Avallone, Martino; Björklund, Tomas; Reggiani, Paula Cecilia; Pardo, Joaquín
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Astrocytes are essential for maintaining neuronal health and regulating the brain's inflammatory environment. In this study, we developed an adeno-associated viral vector (AAV9) designed to selectively overexpress glial cell line-derived neurotrophic factor (GDNF) in astrocytes, using the astrocyte-specific GFAP promoter and TdTomato for transduction tracking. This approach yielded targeted GDNF expression in hippocampal astrocytes. Sholl analysis revealed that GDNF overexpression significantly enhanced astrocytic branching complexity and process length. Using the intracerebroventricular streptozotocin (STZ) model of neurodegeneration, we evaluated the impact of GDNF on astrocytic morphology, neuroinflammation, and hippocampal-dependent memory. Although GDNF prevented astrocytic process length reduction, it did not mitigate neuroinflammation, as evidenced by persistent microglial activation, nor did it improve deficits in the novel object recognition task. However, GDNF + STZ treated animals performed similarly as SHAM controls at exploring the goal sector at the Barnes Maze. These findings demonstrate the capacity of the AAV-GFAP-GDNF-TdTom construct to induce astrocytic branching and partially preserve memory function. They also underscore its partial therapeutic potential in a neuroinflammatory, metabolically compromised and neurodegenerative context.
Instituto de Investigaciones Bioquímicas de La Plata
Materia
Ciencias Médicas
Astrocytes
GDNF
Hippocampus
AAV9
Neurodegeneration
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/193479
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/193479
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat modelVidal Escobedo, Ana AbrilPeralta, FacundoMorel, Gustavo RamónAvallone, MartinoBjörklund, TomasReggiani, Paula CeciliaPardo, JoaquínCiencias MédicasAstrocytesGDNFHippocampusAAV9NeurodegenerationAstrocytes are essential for maintaining neuronal health and regulating the brain's inflammatory environment. In this study, we developed an adeno-associated viral vector (AAV9) designed to selectively overexpress glial cell line-derived neurotrophic factor (GDNF) in astrocytes, using the astrocyte-specific GFAP promoter and TdTomato for transduction tracking. This approach yielded targeted GDNF expression in hippocampal astrocytes. Sholl analysis revealed that GDNF overexpression significantly enhanced astrocytic branching complexity and process length. Using the intracerebroventricular streptozotocin (STZ) model of neurodegeneration, we evaluated the impact of GDNF on astrocytic morphology, neuroinflammation, and hippocampal-dependent memory. Although GDNF prevented astrocytic process length reduction, it did not mitigate neuroinflammation, as evidenced by persistent microglial activation, nor did it improve deficits in the novel object recognition task. However, GDNF + STZ treated animals performed similarly as SHAM controls at exploring the goal sector at the Barnes Maze. These findings demonstrate the capacity of the AAV-GFAP-GDNF-TdTom construct to induce astrocytic branching and partially preserve memory function. They also underscore its partial therapeutic potential in a neuroinflammatory, metabolically compromised and neurodegenerative context.Instituto de Investigaciones Bioquímicas de La Plata2025-06-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://doi.org/10.1038/s41598-025-02881-4http://sedici.unlp.edu.ar/handle/10915/193479enginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-025-02881-4#author-informationinfo:eu-repo/semantics/altIdentifier/issn/2045-2322info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2026-05-06T13:00:49Zoai:sedici.unlp.edu.ar:10915/193479Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292026-05-06 13:00:49.737SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
title GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
spellingShingle GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
Vidal Escobedo, Ana Abril
Ciencias Médicas
Astrocytes
GDNF
Hippocampus
AAV9
Neurodegeneration
title_short GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
title_full GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
title_fullStr GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
title_full_unstemmed GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
title_sort GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer’s rat model
dc.creator.none.fl_str_mv Vidal Escobedo, Ana Abril
Peralta, Facundo
Morel, Gustavo Ramón
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquín
author Vidal Escobedo, Ana Abril
author_facet Vidal Escobedo, Ana Abril
Peralta, Facundo
Morel, Gustavo Ramón
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquín
author_role author
author2 Peralta, Facundo
Morel, Gustavo Ramón
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquín
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Astrocytes
GDNF
Hippocampus
AAV9
Neurodegeneration
topic Ciencias Médicas
Astrocytes
GDNF
Hippocampus
AAV9
Neurodegeneration
dc.description.none.fl_txt_mv Astrocytes are essential for maintaining neuronal health and regulating the brain's inflammatory environment. In this study, we developed an adeno-associated viral vector (AAV9) designed to selectively overexpress glial cell line-derived neurotrophic factor (GDNF) in astrocytes, using the astrocyte-specific GFAP promoter and TdTomato for transduction tracking. This approach yielded targeted GDNF expression in hippocampal astrocytes. Sholl analysis revealed that GDNF overexpression significantly enhanced astrocytic branching complexity and process length. Using the intracerebroventricular streptozotocin (STZ) model of neurodegeneration, we evaluated the impact of GDNF on astrocytic morphology, neuroinflammation, and hippocampal-dependent memory. Although GDNF prevented astrocytic process length reduction, it did not mitigate neuroinflammation, as evidenced by persistent microglial activation, nor did it improve deficits in the novel object recognition task. However, GDNF + STZ treated animals performed similarly as SHAM controls at exploring the goal sector at the Barnes Maze. These findings demonstrate the capacity of the AAV-GFAP-GDNF-TdTom construct to induce astrocytic branching and partially preserve memory function. They also underscore its partial therapeutic potential in a neuroinflammatory, metabolically compromised and neurodegenerative context.
Instituto de Investigaciones Bioquímicas de La Plata
description Astrocytes are essential for maintaining neuronal health and regulating the brain's inflammatory environment. In this study, we developed an adeno-associated viral vector (AAV9) designed to selectively overexpress glial cell line-derived neurotrophic factor (GDNF) in astrocytes, using the astrocyte-specific GFAP promoter and TdTomato for transduction tracking. This approach yielded targeted GDNF expression in hippocampal astrocytes. Sholl analysis revealed that GDNF overexpression significantly enhanced astrocytic branching complexity and process length. Using the intracerebroventricular streptozotocin (STZ) model of neurodegeneration, we evaluated the impact of GDNF on astrocytic morphology, neuroinflammation, and hippocampal-dependent memory. Although GDNF prevented astrocytic process length reduction, it did not mitigate neuroinflammation, as evidenced by persistent microglial activation, nor did it improve deficits in the novel object recognition task. However, GDNF + STZ treated animals performed similarly as SHAM controls at exploring the goal sector at the Barnes Maze. These findings demonstrate the capacity of the AAV-GFAP-GDNF-TdTom construct to induce astrocytic branching and partially preserve memory function. They also underscore its partial therapeutic potential in a neuroinflammatory, metabolically compromised and neurodegenerative context.
publishDate 2025
dc.date.none.fl_str_mv 2025-06-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1038/s41598-025-02881-4
http://sedici.unlp.edu.ar/handle/10915/193479
url https://doi.org/10.1038/s41598-025-02881-4
http://sedici.unlp.edu.ar/handle/10915/193479
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-025-02881-4#author-information
info:eu-repo/semantics/altIdentifier/issn/2045-2322
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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