Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation
Summary: Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes in mice following peripherally induced neuroinflammation...
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doaj-7a09a99f84a34de78b7b3e09787785422021-08-12T04:33:55ZengElsevierCell Reports2211-12472021-08-01366109508Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammationBlanca Diaz-Castro0Alexander M. Bernstein1Giovanni Coppola2Michael V. Sofroniew3Baljit S. Khakh4Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; UK Dementia Research Institute and Centre for Discovery Brain Sciences, University of Edinburgh, Chancellor’s Building, Edinburgh, Scotland EH16 4SB, UK; Corresponding authorDepartment of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USADepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USADepartment of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USADepartment of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; Corresponding authorSummary: Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes in mice following peripherally induced neuroinflammation triggered by a systemic bacterial endotoxin, lipopolysaccharide, which produces sickness-related behaviors, including anhedonia. Neuroinflammation-mediated behavioral changes and astrocyte-specific gene expression alterations peak when anhedonia is greatest and then reverse to normal. Notably, region-specific molecular identities of PFC and VCX astrocytes are largely maintained during reactivity changes. Gene pathway analyses reveal alterations of diverse cell signaling pathways, including changes in cell-cell interactions of multiple cell types that may underlie the central effects of neuroinflammation. Certain astrocyte molecular signatures accompanying neuroinflammation are shared with changes reported in Alzheimer’s disease and mouse models. However, we find no evidence of altered neuronal survival or function in the PFC even when neuroinflammation-induced astrocyte reactivity and behavioral changes are significant.http://www.sciencedirect.com/science/article/pii/S2211124721009384astrocyteneuroinflammationLPSprefrontal cortexastrocyte reactivityRNA-seq |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Blanca Diaz-Castro Alexander M. Bernstein Giovanni Coppola Michael V. Sofroniew Baljit S. Khakh |
spellingShingle |
Blanca Diaz-Castro Alexander M. Bernstein Giovanni Coppola Michael V. Sofroniew Baljit S. Khakh Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation Cell Reports astrocyte neuroinflammation LPS prefrontal cortex astrocyte reactivity RNA-seq |
author_facet |
Blanca Diaz-Castro Alexander M. Bernstein Giovanni Coppola Michael V. Sofroniew Baljit S. Khakh |
author_sort |
Blanca Diaz-Castro |
title |
Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
title_short |
Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
title_full |
Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
title_fullStr |
Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
title_full_unstemmed |
Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
title_sort |
molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-08-01 |
description |
Summary: Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes in mice following peripherally induced neuroinflammation triggered by a systemic bacterial endotoxin, lipopolysaccharide, which produces sickness-related behaviors, including anhedonia. Neuroinflammation-mediated behavioral changes and astrocyte-specific gene expression alterations peak when anhedonia is greatest and then reverse to normal. Notably, region-specific molecular identities of PFC and VCX astrocytes are largely maintained during reactivity changes. Gene pathway analyses reveal alterations of diverse cell signaling pathways, including changes in cell-cell interactions of multiple cell types that may underlie the central effects of neuroinflammation. Certain astrocyte molecular signatures accompanying neuroinflammation are shared with changes reported in Alzheimer’s disease and mouse models. However, we find no evidence of altered neuronal survival or function in the PFC even when neuroinflammation-induced astrocyte reactivity and behavioral changes are significant. |
topic |
astrocyte neuroinflammation LPS prefrontal cortex astrocyte reactivity RNA-seq |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721009384 |
work_keys_str_mv |
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