Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes

Autores
Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Avallone, Martino; Björklund, Tomas; Reggiani, Paula Cecilia; Pardo, Joaquin
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting indisrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressingneurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset ofneurodegeneration.We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards inducedneurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model ofbehavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thoroughtransgene expression along the hippocampus with a single viral injection. Although species typical behavior wasimpaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of thesecells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZcontrol animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1rats.We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individualswith early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.
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: Avallone, Martino. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;
Fil: Björklund, Tomas. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;
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
Alzheimer
IGF1
AAV
Astrocitos
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266793
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266793
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytesPeralta, FacundoVidal Escobedo, Ana AbrilLópez Hanotte, JulietteAvallone, MartinoBjörklund, TomasReggiani, Paula CeciliaPardo, JoaquinAlzheimerIGF1AAVAstrocitoshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting indisrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressingneurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset ofneurodegeneration.We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards inducedneurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model ofbehavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thoroughtransgene expression along the hippocampus with a single viral injection. Although species typical behavior wasimpaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of thesecells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZcontrol animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1rats.We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individualswith early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.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: Avallone, Martino. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;Fil: Björklund, Tomas. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;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"; 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"; ArgentinaAcademic Press Inc Elsevier Science2024-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266793Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Avallone, Martino; Björklund, Tomas; et al.; Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes; Academic Press Inc Elsevier Science; Neurobiology of Disease; 200; 10-2024; 1-130969-9961CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0969996124002122info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2024.106612info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:05:16Zoai:ri.conicet.gov.ar:11336/266793instacron: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:34982025-09-17 11:05:16.399CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
title Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
spellingShingle Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
Peralta, Facundo
Alzheimer
IGF1
AAV
Astrocitos
title_short Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
title_full Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
title_fullStr Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
title_full_unstemmed Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
title_sort Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes
dc.creator.none.fl_str_mv Peralta, Facundo
Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquin
author Peralta, Facundo
author_facet Peralta, Facundo
Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquin
author_role author
author2 Vidal Escobedo, Ana Abril
López Hanotte, Juliette
Avallone, Martino
Björklund, Tomas
Reggiani, Paula Cecilia
Pardo, Joaquin
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer
IGF1
AAV
Astrocitos
topic Alzheimer
IGF1
AAV
Astrocitos
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting indisrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressingneurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset ofneurodegeneration.We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards inducedneurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model ofbehavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thoroughtransgene expression along the hippocampus with a single viral injection. Although species typical behavior wasimpaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of thesecells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZcontrol animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1rats.We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individualswith early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.
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: Avallone, Martino. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;
Fil: Björklund, Tomas. Department Of Experimental Medical Science ; Faculty Of Medicine ; Lund University;
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 Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting indisrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressingneurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset ofneurodegeneration.We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards inducedneurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model ofbehavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thoroughtransgene expression along the hippocampus with a single viral injection. Although species typical behavior wasimpaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of thesecells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZcontrol animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1rats.We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individualswith early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.
publishDate 2024
dc.date.none.fl_str_mv 2024-10
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/11336/266793
Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Avallone, Martino; Björklund, Tomas; et al.; Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes; Academic Press Inc Elsevier Science; Neurobiology of Disease; 200; 10-2024; 1-13
0969-9961
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266793
identifier_str_mv Peralta, Facundo; Vidal Escobedo, Ana Abril; López Hanotte, Juliette; Avallone, Martino; Björklund, Tomas; et al.; Preventive cognitive protection based on AAV9 overexpression of IGF1 in hippocampal astrocytes; Academic Press Inc Elsevier Science; Neurobiology of Disease; 200; 10-2024; 1-13
0969-9961
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://linkinghub.elsevier.com/retrieve/pii/S0969996124002122
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2024.106612
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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score 13.001348

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