Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes

Autores
Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Zappa Villar, María Florencia; Reggiani, Paula Cecilia; Pardo, Joaquin
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
*PCR and JP have equal contribution in this work. Background: Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegener-ative disease. The cerebral histopathological study shows that the hippocampus (Hc) isseverely affected and presents marked astroglial reactivity and in consequence, neu-ronal trophic support decreases. We set out to develop an astrocyte-targeted therapythat prevents the detrimental actions of reactive astrocytes, enhance their neuropro-tection, and restore their modulatory properties in our sAD rat model mediated by theintracerebroventricular (icv) injection of streptozotocin (STZ).Method: AAV generation: Bicistronic serotype 9 adeno-associated viruses (AAVs)driven by the gfaABC1D promoter (astrocyte specific) [Lee et al 2008. https://doi.org/10.1002/glia.20622] were generated by the 3-plasmid system. Two vectors harbouringthe cassettes gfaABC1D-IGF1-ires-tdTomato (AAV-IGF1) and gfaABC1D-GFP-ires-tdTomato (AAV-GFP) were constructed. AAVs characterization was performed byRT-qPCR and immunohistochemistry (IHC). Gene therapy in Hc with AAV-IGF1: Youngmale rats were used and divided into 3 groups: SHAM, GFP and IGF1. On Experi-mental Day (ED) -28, animals received bilateral injections of artificial cerebrospinalfluid (aCSF) (SHAM) or AAV-GFP/IGF1(GFP/IGF1). At ED 0, animals received icv aCSF(SHAM) or STZ (GFP/IGF1) (3mg/kg) bilaterally. Among the ED +17/+26 behaviouraltests were performed (Open Field Test, Novel Object Recognition Test, and BarnesMaze).Result: Transgenes overexpression was confirmed by RT-qPCR and IHC. Vectors speci-ficity was determined since 100% of the cells with red fluorescence (tdTomato+)were GFAP+. We also observed that a single injection of the vector is sufficient totransduce Hc throughout its rostro caudal extension. Animals belonging to the AAV-GFP+STZ group showed a significant deterioration in the behavioural tests, whileAAV-IGF1+STZ animals did not show significant differences compared with the SHAMcontrol in tested behaviours. Conclusion: We explored a targeted therapeutic approach with high specificity tohippocampal astrocytes, which allowed us to modulate astrocyte IGF1 expression,thus promoting neuroprotective effects and preventing behavioural decline in ani-mals with sAD. Consequently, our results are encouraging and suggest that astrocytemanipulation can be approached as a promising therapeutic means.
Fil: Peralta, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Vidal Escobedo, Ana Abril. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: López Hanotte, Juliette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Zappa Villar, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Materia
ASTROCYTE
IGF1
GENE THERAPY
STREPTOZOTOCIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/250448
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/250448
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytesPeralta, FacundoVidal Escobedo, Ana AbrilLópez Hanotte, JulietteZappa Villar, María FlorenciaReggiani, Paula CeciliaPardo, JoaquinASTROCYTEIGF1GENE THERAPYSTREPTOZOTOCINhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3*PCR and JP have equal contribution in this work. Background: Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegener-ative disease. The cerebral histopathological study shows that the hippocampus (Hc) isseverely affected and presents marked astroglial reactivity and in consequence, neu-ronal trophic support decreases. We set out to develop an astrocyte-targeted therapythat prevents the detrimental actions of reactive astrocytes, enhance their neuropro-tection, and restore their modulatory properties in our sAD rat model mediated by theintracerebroventricular (icv) injection of streptozotocin (STZ).Method: AAV generation: Bicistronic serotype 9 adeno-associated viruses (AAVs)driven by the gfaABC1D promoter (astrocyte specific) [Lee et al 2008. https://doi.org/10.1002/glia.20622] were generated by the 3-plasmid system. Two vectors harbouringthe cassettes gfaABC1D-IGF1-ires-tdTomato (AAV-IGF1) and gfaABC1D-GFP-ires-tdTomato (AAV-GFP) were constructed. AAVs characterization was performed byRT-qPCR and immunohistochemistry (IHC). Gene therapy in Hc with AAV-IGF1: Youngmale rats were used and divided into 3 groups: SHAM, GFP and IGF1. On Experi-mental Day (ED) -28, animals received bilateral injections of artificial cerebrospinalfluid (aCSF) (SHAM) or AAV-GFP/IGF1(GFP/IGF1). At ED 0, animals received icv aCSF(SHAM) or STZ (GFP/IGF1) (3mg/kg) bilaterally. Among the ED +17/+26 behaviouraltests were performed (Open Field Test, Novel Object Recognition Test, and BarnesMaze).Result: Transgenes overexpression was confirmed by RT-qPCR and IHC. Vectors speci-ficity was determined since 100% of the cells with red fluorescence (tdTomato+)were GFAP+. We also observed that a single injection of the vector is sufficient totransduce Hc throughout its rostro caudal extension. Animals belonging to the AAV-GFP+STZ group showed a significant deterioration in the behavioural tests, whileAAV-IGF1+STZ animals did not show significant differences compared with the SHAMcontrol in tested behaviours. Conclusion: We explored a targeted therapeutic approach with high specificity tohippocampal astrocytes, which allowed us to modulate astrocyte IGF1 expression,thus promoting neuroprotective effects and preventing behavioural decline in ani-mals with sAD. Consequently, our results are encouraging and suggest that astrocytemanipulation can be approached as a promising therapeutic means.Fil: Peralta, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Vidal Escobedo, Ana Abril. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: López Hanotte, Juliette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Zappa Villar, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaElsevier Science Inc.2023-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/250448Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Zappa Villar, María Florencia; Reggiani, Paula Cecilia; et al.; Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes; Elsevier Science Inc.; Alzheimers & Dementia; 19; S13; 12-2023; 1-21552-5260CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.077445info:eu-repo/semantics/altIdentifier/doi/10.1002/alz.077445info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:35:37Zoai:ri.conicet.gov.ar:11336/250448instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:35:37.651CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
title Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
spellingShingle Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
Peralta, Facundo
ASTROCYTE
IGF1
GENE THERAPY
STREPTOZOTOCIN
title_short Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
title_full Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
title_fullStr Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
title_full_unstemmed Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
title_sort Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes
dc.creator.none.fl_str_mv Peralta, Facundo
Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Zappa Villar, María Florencia
Reggiani, Paula Cecilia
Pardo, Joaquin
author Peralta, Facundo
author_facet Peralta, Facundo
Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Zappa Villar, María Florencia
Reggiani, Paula Cecilia
Pardo, Joaquin
author_role author
author2 Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Zappa Villar, María Florencia
Reggiani, Paula Cecilia
Pardo, Joaquin
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ASTROCYTE
IGF1
GENE THERAPY
STREPTOZOTOCIN
topic ASTROCYTE
IGF1
GENE THERAPY
STREPTOZOTOCIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv *PCR and JP have equal contribution in this work. Background: Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegener-ative disease. The cerebral histopathological study shows that the hippocampus (Hc) isseverely affected and presents marked astroglial reactivity and in consequence, neu-ronal trophic support decreases. We set out to develop an astrocyte-targeted therapythat prevents the detrimental actions of reactive astrocytes, enhance their neuropro-tection, and restore their modulatory properties in our sAD rat model mediated by theintracerebroventricular (icv) injection of streptozotocin (STZ).Method: AAV generation: Bicistronic serotype 9 adeno-associated viruses (AAVs)driven by the gfaABC1D promoter (astrocyte specific) [Lee et al 2008. https://doi.org/10.1002/glia.20622] were generated by the 3-plasmid system. Two vectors harbouringthe cassettes gfaABC1D-IGF1-ires-tdTomato (AAV-IGF1) and gfaABC1D-GFP-ires-tdTomato (AAV-GFP) were constructed. AAVs characterization was performed byRT-qPCR and immunohistochemistry (IHC). Gene therapy in Hc with AAV-IGF1: Youngmale rats were used and divided into 3 groups: SHAM, GFP and IGF1. On Experi-mental Day (ED) -28, animals received bilateral injections of artificial cerebrospinalfluid (aCSF) (SHAM) or AAV-GFP/IGF1(GFP/IGF1). At ED 0, animals received icv aCSF(SHAM) or STZ (GFP/IGF1) (3mg/kg) bilaterally. Among the ED +17/+26 behaviouraltests were performed (Open Field Test, Novel Object Recognition Test, and BarnesMaze).Result: Transgenes overexpression was confirmed by RT-qPCR and IHC. Vectors speci-ficity was determined since 100% of the cells with red fluorescence (tdTomato+)were GFAP+. We also observed that a single injection of the vector is sufficient totransduce Hc throughout its rostro caudal extension. Animals belonging to the AAV-GFP+STZ group showed a significant deterioration in the behavioural tests, whileAAV-IGF1+STZ animals did not show significant differences compared with the SHAMcontrol in tested behaviours. Conclusion: We explored a targeted therapeutic approach with high specificity tohippocampal astrocytes, which allowed us to modulate astrocyte IGF1 expression,thus promoting neuroprotective effects and preventing behavioural decline in ani-mals with sAD. Consequently, our results are encouraging and suggest that astrocytemanipulation can be approached as a promising therapeutic means.
Fil: Peralta, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Vidal Escobedo, Ana Abril. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: López Hanotte, Juliette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Zappa Villar, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
description *PCR and JP have equal contribution in this work. Background: Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegener-ative disease. The cerebral histopathological study shows that the hippocampus (Hc) isseverely affected and presents marked astroglial reactivity and in consequence, neu-ronal trophic support decreases. We set out to develop an astrocyte-targeted therapythat prevents the detrimental actions of reactive astrocytes, enhance their neuropro-tection, and restore their modulatory properties in our sAD rat model mediated by theintracerebroventricular (icv) injection of streptozotocin (STZ).Method: AAV generation: Bicistronic serotype 9 adeno-associated viruses (AAVs)driven by the gfaABC1D promoter (astrocyte specific) [Lee et al 2008. https://doi.org/10.1002/glia.20622] were generated by the 3-plasmid system. Two vectors harbouringthe cassettes gfaABC1D-IGF1-ires-tdTomato (AAV-IGF1) and gfaABC1D-GFP-ires-tdTomato (AAV-GFP) were constructed. AAVs characterization was performed byRT-qPCR and immunohistochemistry (IHC). Gene therapy in Hc with AAV-IGF1: Youngmale rats were used and divided into 3 groups: SHAM, GFP and IGF1. On Experi-mental Day (ED) -28, animals received bilateral injections of artificial cerebrospinalfluid (aCSF) (SHAM) or AAV-GFP/IGF1(GFP/IGF1). At ED 0, animals received icv aCSF(SHAM) or STZ (GFP/IGF1) (3mg/kg) bilaterally. Among the ED +17/+26 behaviouraltests were performed (Open Field Test, Novel Object Recognition Test, and BarnesMaze).Result: Transgenes overexpression was confirmed by RT-qPCR and IHC. Vectors speci-ficity was determined since 100% of the cells with red fluorescence (tdTomato+)were GFAP+. We also observed that a single injection of the vector is sufficient totransduce Hc throughout its rostro caudal extension. Animals belonging to the AAV-GFP+STZ group showed a significant deterioration in the behavioural tests, whileAAV-IGF1+STZ animals did not show significant differences compared with the SHAMcontrol in tested behaviours. Conclusion: We explored a targeted therapeutic approach with high specificity tohippocampal astrocytes, which allowed us to modulate astrocyte IGF1 expression,thus promoting neuroprotective effects and preventing behavioural decline in ani-mals with sAD. Consequently, our results are encouraging and suggest that astrocytemanipulation can be approached as a promising therapeutic means.
publishDate 2023
dc.date.none.fl_str_mv 2023-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/250448
Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Zappa Villar, María Florencia; Reggiani, Paula Cecilia; et al.; Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes; Elsevier Science Inc.; Alzheimers & Dementia; 19; S13; 12-2023; 1-2
1552-5260
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250448
identifier_str_mv Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Zappa Villar, María Florencia; Reggiani, Paula Cecilia; et al.; Highly specific gene therapy in a rat model of sporadic Alzheimer’s disease: use of adeno‐associated viral vectors to overexpress IGF1 in hippocampal astrocytes; Elsevier Science Inc.; Alzheimers & Dementia; 19; S13; 12-2023; 1-2
1552-5260
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.077445
info:eu-repo/semantics/altIdentifier/doi/10.1002/alz.077445
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc.
publisher.none.fl_str_mv Elsevier Science Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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