IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, m...

Descripción completa

Detalles Bibliográficos
Autores principales: Falomir Lockhart, Eugenia, Dolcetti, Franco Juan Cruz, Herrera, Macarena Lorena, Pennini, Jerónimo, Zappa Villar, María Florencia, Salinas, Gabriela, Portiansky, Enrique Leo, Spittau, Björn, Lacunza, Ezequiel, Hereñú, Claudia Beatriz, Bellini, María José
Formato: Articulo Preprint
Lenguaje:Español
Publicado: 2021
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/126606
Aporte de:
id I19-R120-10915-126606
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Español
topic Biología
Genetic enhancement
Internal medicine
Endocrinology
Gene expression
Caudate putamen
Rat brain
Biology
spellingShingle Biología
Genetic enhancement
Internal medicine
Endocrinology
Gene expression
Caudate putamen
Rat brain
Biology
Falomir Lockhart, Eugenia
Dolcetti, Franco Juan Cruz
Herrera, Macarena Lorena
Pennini, Jerónimo
Zappa Villar, María Florencia
Salinas, Gabriela
Portiansky, Enrique Leo
Spittau, Björn
Lacunza, Ezequiel
Hereñú, Claudia Beatriz
Bellini, María José
IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
topic_facet Biología
Genetic enhancement
Internal medicine
Endocrinology
Gene expression
Caudate putamen
Rat brain
Biology
description Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergo a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of microglia senescence is of great relevance to understand age‐related declines in cognitive and motor function.We have targeted the deleterious effects of aging by implementing gene therapy with IGF-1, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) IGF-1 gene therapy on aged female rats and evaluated its effect on Caudate-Putamen unit (CPu) gene expression and inflammatory state. IGF-1 gene therapy modified senescent microglia of the CPu towards an anti-inflammatory state increasing the proportion of Iba1<jats:sup>+</jats:sup>Arg1<jats:sup>+</jats:sup> cells. Moreover, IGF-1 gene therapy was able to regulate the pro-inflammatory environment of CPu in female aged rats by down-regulating the expression of genes typically over-expressed during aging. Our results demonstrate that, ICV IGF-1 gene therapy, is capable to modulate microglia cells and CPu gene expression, leading to an improvement in motor function.
format Articulo
Preprint
author Falomir Lockhart, Eugenia
Dolcetti, Franco Juan Cruz
Herrera, Macarena Lorena
Pennini, Jerónimo
Zappa Villar, María Florencia
Salinas, Gabriela
Portiansky, Enrique Leo
Spittau, Björn
Lacunza, Ezequiel
Hereñú, Claudia Beatriz
Bellini, María José
author_facet Falomir Lockhart, Eugenia
Dolcetti, Franco Juan Cruz
Herrera, Macarena Lorena
Pennini, Jerónimo
Zappa Villar, María Florencia
Salinas, Gabriela
Portiansky, Enrique Leo
Spittau, Björn
Lacunza, Ezequiel
Hereñú, Claudia Beatriz
Bellini, María José
author_sort Falomir Lockhart, Eugenia
title IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
title_short IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
title_full IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
title_fullStr IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
title_full_unstemmed IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain
title_sort igf-1 gene therapy modifies inflammatory environment and gene expression in the caudate-putamen of aged female rat brain
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/126606
work_keys_str_mv AT falomirlockharteugenia igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT dolcettifrancojuancruz igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT herreramacarenalorena igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT penninijeronimo igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT zappavillarmariaflorencia igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT salinasgabriela igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT portianskyenriqueleo igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT spittaubjorn igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT lacunzaezequiel igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT herenuclaudiabeatriz igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
AT bellinimariajose igf1genetherapymodifiesinflammatoryenvironmentandgeneexpressioninthecaudateputamenofagedfemaleratbrain
bdutipo_str Repositorios
_version_ 1764820450919055360