Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats

Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scar...

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Main Authors: Claire Deckers, Reza Karbalaei, Nylah A. Miles, Eden V. Harder, Emily Witt, Erin P. Harris, Kathryn Reissner, Mathieu E. Wimmer, Debra A. Bangasser
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Neurobiology of Stress
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352289524000031
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author Claire Deckers
Reza Karbalaei
Nylah A. Miles
Eden V. Harder
Emily Witt
Erin P. Harris
Kathryn Reissner
Mathieu E. Wimmer
Debra A. Bangasser
author_facet Claire Deckers
Reza Karbalaei
Nylah A. Miles
Eden V. Harder
Emily Witt
Erin P. Harris
Kathryn Reissner
Mathieu E. Wimmer
Debra A. Bangasser
author_sort Claire Deckers
collection DOAJ
description Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scarcity, the limited bedding and nesting (LBN) manipulation, in rats. We previously found that LBN augments maternal behaviors and promotes later resilience to adult addiction-related behaviors, reducing impulsivity, risky decision-making, and morphine self-administration. These behaviors rely on glutamatergic transmission in the medial orbitofrontal (mOFC) and medial prefrontal (mPFC) cortex. Here we tested whether LBN changed astrocyte morphology in the mOFC and mPFC of adult rats using a novel viral approach that, unlike traditional markers, fully labels astrocytes. Prior exposure to LBN causes an increase in the surface area and volume of astrocytes in the mOFC and mPFC of adult males and females relative to control-raised rats. We next used bulk RNA sequencing of OFC tissue to assess transcriptional changes that could increase astrocyte size in LBN rats. LBN caused mainly sex-specific changes in differentially expressed genes. Pathway analysis revealed that OFC glutamatergic signaling is altered by LBN in males and females, but the gene changes in that pathway differed across sex. This may represent a convergent sex difference where glutamatergic signaling, which affects astrocyte morphology, is altered by LBN via sex-specific mechanisms. Collectively, these studies highlight that astrocytes may be an important cell type that mediates the effect of early resource scarcity on adult brain function.
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spelling doaj.art-2702bf6b80a34e60a21513a72f46053b2024-03-18T04:33:59ZengElsevierNeurobiology of Stress2352-28952024-03-0129100607Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult ratsClaire Deckers0Reza Karbalaei1Nylah A. Miles2Eden V. Harder3Emily Witt4Erin P. Harris5Kathryn Reissner6Mathieu E. Wimmer7Debra A. Bangasser8Department of Psychology and Neuroscience Program, Temple University, Philadelphia, USADepartment of Psychology and Neuroscience Program, Temple University, Philadelphia, USADepartment of Psychology and Neuroscience Program, Temple University, Philadelphia, USADepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USANeuroscience Institute, Georgia State University, Atlanta, USA; Center for Behavioral Neuroscience, Georgia State University, Atlanta, USADepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment of Psychology and Neuroscience Program, Temple University, Philadelphia, USADepartment of Psychology and Neuroscience Program, Temple University, Philadelphia, USA; Neuroscience Institute, Georgia State University, Atlanta, USA; Center for Behavioral Neuroscience, Georgia State University, Atlanta, USA; Corresponding author. Georgia State University, 100 Piedmont Ave, SE, Atlanta, GA, 30303, USA.Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scarcity, the limited bedding and nesting (LBN) manipulation, in rats. We previously found that LBN augments maternal behaviors and promotes later resilience to adult addiction-related behaviors, reducing impulsivity, risky decision-making, and morphine self-administration. These behaviors rely on glutamatergic transmission in the medial orbitofrontal (mOFC) and medial prefrontal (mPFC) cortex. Here we tested whether LBN changed astrocyte morphology in the mOFC and mPFC of adult rats using a novel viral approach that, unlike traditional markers, fully labels astrocytes. Prior exposure to LBN causes an increase in the surface area and volume of astrocytes in the mOFC and mPFC of adult males and females relative to control-raised rats. We next used bulk RNA sequencing of OFC tissue to assess transcriptional changes that could increase astrocyte size in LBN rats. LBN caused mainly sex-specific changes in differentially expressed genes. Pathway analysis revealed that OFC glutamatergic signaling is altered by LBN in males and females, but the gene changes in that pathway differed across sex. This may represent a convergent sex difference where glutamatergic signaling, which affects astrocyte morphology, is altered by LBN via sex-specific mechanisms. Collectively, these studies highlight that astrocytes may be an important cell type that mediates the effect of early resource scarcity on adult brain function.http://www.sciencedirect.com/science/article/pii/S2352289524000031GliaStressMorphologyGlutamateSex differencesCortex
spellingShingle Claire Deckers
Reza Karbalaei
Nylah A. Miles
Eden V. Harder
Emily Witt
Erin P. Harris
Kathryn Reissner
Mathieu E. Wimmer
Debra A. Bangasser
Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
Neurobiology of Stress
Glia
Stress
Morphology
Glutamate
Sex differences
Cortex
title Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
title_full Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
title_fullStr Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
title_full_unstemmed Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
title_short Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats
title_sort early resource scarcity causes cortical astrocyte enlargement and sex specific changes in the orbitofrontal cortex transcriptome in adult rats
topic Glia
Stress
Morphology
Glutamate
Sex differences
Cortex
url http://www.sciencedirect.com/science/article/pii/S2352289524000031
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