Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation
Abstract Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is know...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02827-5 |
| _version_ | 1797789623454269440 |
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| author | Joshua D. Samuels Madison L. Lotstein Michael L. Lehmann Abdel G. Elkahloun Subhadra Banerjee Miles Herkenham |
| author_facet | Joshua D. Samuels Madison L. Lotstein Michael L. Lehmann Abdel G. Elkahloun Subhadra Banerjee Miles Herkenham |
| author_sort | Joshua D. Samuels |
| collection | DOAJ |
| description | Abstract Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the isolated cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to non-stress, home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology. |
| first_indexed | 2024-03-13T01:53:18Z |
| format | Article |
| id | doaj.art-39de998efab140ad9e3cecf5e5a8ce04 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-13T01:53:18Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-39de998efab140ad9e3cecf5e5a8ce042023-07-02T11:21:43ZengBMCJournal of Neuroinflammation1742-20942023-06-0120111610.1186/s12974-023-02827-5Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activationJoshua D. Samuels0Madison L. Lotstein1Michael L. Lehmann2Abdel G. Elkahloun3Subhadra Banerjee4Miles Herkenham5Section on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, National Institutes of HealthSection on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, National Institutes of HealthSection on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, National Institutes of HealthCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of HealthFlow Cytometry Core, Laboratory of Genome Integrity, National Cancer Institute, National Institutes of HealthSection on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, National Institutes of HealthAbstract Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the isolated cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to non-stress, home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology.https://doi.org/10.1186/s12974-023-02827-5Single-cell RNA sequencingCerebrovasculaturePsychosocial stressVascular repairImmune activation |
| spellingShingle | Joshua D. Samuels Madison L. Lotstein Michael L. Lehmann Abdel G. Elkahloun Subhadra Banerjee Miles Herkenham Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation Journal of Neuroinflammation Single-cell RNA sequencing Cerebrovasculature Psychosocial stress Vascular repair Immune activation |
| title | Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| title_full | Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| title_fullStr | Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| title_full_unstemmed | Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| title_short | Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| title_sort | chronic social defeat alters brain vascular associated cell gene expression patterns leading to vascular dysfunction and immune system activation |
| topic | Single-cell RNA sequencing Cerebrovasculature Psychosocial stress Vascular repair Immune activation |
| url | https://doi.org/10.1186/s12974-023-02827-5 |
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