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Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure

Fetal microglia that are particularly sensitive cells to the changes in utero environment might be involved in the sex-biased onset and vulnerability to psychiatric disorders. To address this issue, we administered a 50 µg/kg dexamethasone (DEX) to dams subcutaneously from gestational days 16 to 18...

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Autores principales: Rim, Chan, Park, Hyun-Sun, You, Min-Jung, Yang, Bohyun, Kim, Hui-Ju, Sung, Soyoung, Kwon, Min-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458670/
https://www.ncbi.nlm.nih.gov/pubmed/36075925
http://dx.doi.org/10.1038/s41537-022-00280-6
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author Rim, Chan
Park, Hyun-Sun
You, Min-Jung
Yang, Bohyun
Kim, Hui-Ju
Sung, Soyoung
Kwon, Min-Soo
author_facet Rim, Chan
Park, Hyun-Sun
You, Min-Jung
Yang, Bohyun
Kim, Hui-Ju
Sung, Soyoung
Kwon, Min-Soo
author_sort Rim, Chan
collection PubMed
description Fetal microglia that are particularly sensitive cells to the changes in utero environment might be involved in the sex-biased onset and vulnerability to psychiatric disorders. To address this issue, we administered a 50 µg/kg dexamethasone (DEX) to dams subcutaneously from gestational days 16 to 18 and a series of behavioral assessments were performed in the offspring. Prenatal exposure to dexamethasone (PN-DEX) induced schizophrenia (SCZ)-relevant behaviors in male mice and depressive-like behavior in female mice. SCZ-relevant behavioral patterns occurred in 10-week-old (10 W) male mice but not in 4-week-old (4 W) male mice. Microglia in the medial prefrontal cortex (mPFC) and the striatum (STR) of 10 W males prenatally treated with dexamethasone (10 W PN-DEX-M) showed hyper-ramified morphology and dramatically reduced spine density in mPFC. Immunofluorescence studies indicated that microglia in the mPFC of the 10 W PN-DEX-M group interacted with pre-synaptic Bassoon and post-synaptic density 95 (PSD95) puncta. PN-DEX-M also showed significantly changed dopamine system proteins. However, a testosterone surge during adolescence was not a trigger on SCZ-relevant behavior occurrence in 10 W PN-DEX-M. Furthermore, females prenatally treated with dexamethasone (PN-DEX-F) displayed depressive-like behavior, in addition to HPA-axis activation and inflammatory microglial phenotypes in their hippocampus (HPC). We propose that altered microglial function, such as increased synaptic pruning, may be involved in the occurrence of SCZ-relevant behavior in PN-DEX-M and sex-biased abnormal behavior in the PN-DEX model.
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spelling pubmed-94586702022-09-10 Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure Rim, Chan Park, Hyun-Sun You, Min-Jung Yang, Bohyun Kim, Hui-Ju Sung, Soyoung Kwon, Min-Soo Schizophrenia (Heidelb) Article Fetal microglia that are particularly sensitive cells to the changes in utero environment might be involved in the sex-biased onset and vulnerability to psychiatric disorders. To address this issue, we administered a 50 µg/kg dexamethasone (DEX) to dams subcutaneously from gestational days 16 to 18 and a series of behavioral assessments were performed in the offspring. Prenatal exposure to dexamethasone (PN-DEX) induced schizophrenia (SCZ)-relevant behaviors in male mice and depressive-like behavior in female mice. SCZ-relevant behavioral patterns occurred in 10-week-old (10 W) male mice but not in 4-week-old (4 W) male mice. Microglia in the medial prefrontal cortex (mPFC) and the striatum (STR) of 10 W males prenatally treated with dexamethasone (10 W PN-DEX-M) showed hyper-ramified morphology and dramatically reduced spine density in mPFC. Immunofluorescence studies indicated that microglia in the mPFC of the 10 W PN-DEX-M group interacted with pre-synaptic Bassoon and post-synaptic density 95 (PSD95) puncta. PN-DEX-M also showed significantly changed dopamine system proteins. However, a testosterone surge during adolescence was not a trigger on SCZ-relevant behavior occurrence in 10 W PN-DEX-M. Furthermore, females prenatally treated with dexamethasone (PN-DEX-F) displayed depressive-like behavior, in addition to HPA-axis activation and inflammatory microglial phenotypes in their hippocampus (HPC). We propose that altered microglial function, such as increased synaptic pruning, may be involved in the occurrence of SCZ-relevant behavior in PN-DEX-M and sex-biased abnormal behavior in the PN-DEX model. Nature Publishing Group UK 2022-09-08 /pmc/articles/PMC9458670/ /pubmed/36075925 http://dx.doi.org/10.1038/s41537-022-00280-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rim, Chan
Park, Hyun-Sun
You, Min-Jung
Yang, Bohyun
Kim, Hui-Ju
Sung, Soyoung
Kwon, Min-Soo
Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title_full Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title_fullStr Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title_full_unstemmed Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title_short Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
title_sort microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458670/
https://www.ncbi.nlm.nih.gov/pubmed/36075925
http://dx.doi.org/10.1038/s41537-022-00280-6
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