Neonatal testosterone voids sexually differentiated microglia morphology and behavior

The involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxi...

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Main Authors: Carla Filipa Simões-Henriques, A. Catarina Rodrigues-Neves, Fábio J. Sousa, Rita Gaspar, Inês Almeida, Filipa I. Baptista, António F. Ambrósio, Catarina A. Gomes
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1102068/full
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author Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
Fábio J. Sousa
Fábio J. Sousa
Fábio J. Sousa
Rita Gaspar
Rita Gaspar
Rita Gaspar
Inês Almeida
Inês Almeida
Inês Almeida
Filipa I. Baptista
Filipa I. Baptista
Filipa I. Baptista
António F. Ambrósio
António F. Ambrósio
António F. Ambrósio
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
author_facet Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
Fábio J. Sousa
Fábio J. Sousa
Fábio J. Sousa
Rita Gaspar
Rita Gaspar
Rita Gaspar
Inês Almeida
Inês Almeida
Inês Almeida
Filipa I. Baptista
Filipa I. Baptista
Filipa I. Baptista
António F. Ambrósio
António F. Ambrósio
António F. Ambrósio
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
author_sort Carla Filipa Simões-Henriques
collection DOAJ
description The involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxiety, including the pre-frontal cortex. These physiologic differences likely drive sex-dependent patterns of microglia morphologic remodeling in response to varied stress conditions in different periods of life, that correlate with sex-dependent behavioral adaptation to anxiogenic stimuli. The time-window of appearance of sex differences in microglia, correlating with sex-specific behavioral performance in anxiogenic conditions are still unknown. In rodents, a postnatal peak of the sexual hormone testosterone is determinant for the so-called brain masculinization and sex-determined behavioral traits. In the present work we aim to clarify if differences in microglia morphology are present at birth or can be driven by postnatal testosterone and impacts on the ability to deal with an anxiogenic context. Differences in microglia morphology are not present at birth, but are observable at adolescence (increased complexity of male microglia, particularly in branches more proximal to the soma), when differences in behavior are also observed. Our data also show that adolescent females neonatally treated with testosterone exhibit masculinized microglia and behavior. Importantly, between adolescence and adulthood, a sex-determined shift in the pattern of complexity takes place and microglia from females become more complex. When testosterone is administered, this morphological effect is partially abolished, approximating microglia and behavior to the male phenotype.
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spelling doaj.art-687e04dfefae464797f0beeea699c0fa2023-02-28T13:52:29ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11020681102068Neonatal testosterone voids sexually differentiated microglia morphology and behaviorCarla Filipa Simões-Henriques0Carla Filipa Simões-Henriques1Carla Filipa Simões-Henriques2A. Catarina Rodrigues-Neves3A. Catarina Rodrigues-Neves4A. Catarina Rodrigues-Neves5Fábio J. Sousa6Fábio J. Sousa7Fábio J. Sousa8Rita Gaspar9Rita Gaspar10Rita Gaspar11Inês Almeida12Inês Almeida13Inês Almeida14Filipa I. Baptista15Filipa I. Baptista16Filipa I. Baptista17António F. Ambrósio18António F. Ambrósio19António F. Ambrósio20Catarina A. Gomes21Catarina A. Gomes22Catarina A. Gomes23Catarina A. Gomes24Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, PortugalCenter for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, PortugalClinical Academic Center of Coimbra (CACC), Coimbra, PortugalFaculty of Pharmacy, University of Coimbra, Coimbra, PortugalThe involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxiety, including the pre-frontal cortex. These physiologic differences likely drive sex-dependent patterns of microglia morphologic remodeling in response to varied stress conditions in different periods of life, that correlate with sex-dependent behavioral adaptation to anxiogenic stimuli. The time-window of appearance of sex differences in microglia, correlating with sex-specific behavioral performance in anxiogenic conditions are still unknown. In rodents, a postnatal peak of the sexual hormone testosterone is determinant for the so-called brain masculinization and sex-determined behavioral traits. In the present work we aim to clarify if differences in microglia morphology are present at birth or can be driven by postnatal testosterone and impacts on the ability to deal with an anxiogenic context. Differences in microglia morphology are not present at birth, but are observable at adolescence (increased complexity of male microglia, particularly in branches more proximal to the soma), when differences in behavior are also observed. Our data also show that adolescent females neonatally treated with testosterone exhibit masculinized microglia and behavior. Importantly, between adolescence and adulthood, a sex-determined shift in the pattern of complexity takes place and microglia from females become more complex. When testosterone is administered, this morphological effect is partially abolished, approximating microglia and behavior to the male phenotype.https://www.frontiersin.org/articles/10.3389/fendo.2023.1102068/fulltestosteronemicrogliaanxiety-like behaviorsexorganizational effect
spellingShingle Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
Carla Filipa Simões-Henriques
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
A. Catarina Rodrigues-Neves
Fábio J. Sousa
Fábio J. Sousa
Fábio J. Sousa
Rita Gaspar
Rita Gaspar
Rita Gaspar
Inês Almeida
Inês Almeida
Inês Almeida
Filipa I. Baptista
Filipa I. Baptista
Filipa I. Baptista
António F. Ambrósio
António F. Ambrósio
António F. Ambrósio
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
Catarina A. Gomes
Neonatal testosterone voids sexually differentiated microglia morphology and behavior
Frontiers in Endocrinology
testosterone
microglia
anxiety-like behavior
sex
organizational effect
title Neonatal testosterone voids sexually differentiated microglia morphology and behavior
title_full Neonatal testosterone voids sexually differentiated microglia morphology and behavior
title_fullStr Neonatal testosterone voids sexually differentiated microglia morphology and behavior
title_full_unstemmed Neonatal testosterone voids sexually differentiated microglia morphology and behavior
title_short Neonatal testosterone voids sexually differentiated microglia morphology and behavior
title_sort neonatal testosterone voids sexually differentiated microglia morphology and behavior
topic testosterone
microglia
anxiety-like behavior
sex
organizational effect
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1102068/full
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