Pericytes modulate brain vascular integrity in social stress and depression Article Swipe
Caroline Ménard
,
Laurence Dion‐Albert
,
Alice Cadoret
,
José L. Solano
,
Pavel Kotchetkov
,
Luca Pancotti
,
Sam E.J. Paton
,
Jared VanderZwaag
,
Adeline Collignon
,
Luisa Bandeira Binder
,
Raleigh M. Linville
,
Émanuelle Richer
,
Manon Lebel
,
Signature Consortium
,
Myriam Heiman
,
Marie‐Ève Tremblay
,
Christophe D. Proulx
,
Gustavo Turecki
,
Naguib Mechawar
,
Baptiste Lacoste
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-5060339/v1
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-5060339/v1
Major depressive disorder (MDD) is a leading cause of disease burden worldwide with low therapeutic efficacy. The blood-brain barrier (BBB) is essential to maintain brain homeostasis and regulate drug delivery. Chronic social stress, MDD’s main environmental risk factor, is associated with neurovascular pathology in mice including loss of BBB integrity in mood-regulating brain regions in a sex-specific manner, which is also observed in individuals with MDD. Pericytes ensheathe endothelial cells and modulate BBB functions under physiological and pathological conditions, but contribution of these mural cells in stress responses or mood disorders pathogenesis is unknown. Here, we report profound transcriptomic, morphological and functional alterations in pericytes in the prefrontal cortex (PFC) following stress exposure in female mice and women with MDD. Endothelial cell-to-pericyte crosstalk via PDGFB:PDGFRB signaling is critical for BBB dynamics and proper brain function. Targeted ablation of pericytes in the PFC induced anxiety- and depression-like behaviours in mice, while viral-mediated increase in pericyte-endothelial communication promoted stress coping behaviors. RNA-seq of human brain endothelial cells and pericytes exposed to MDD serum revealed changes in extracellular matrix-related genes and cell-cell communication. PDGF-BB serum level correlated with depressive symptoms and diagnosis. Altogether, our findings shed light on a novel mechanism underlying PFC dysfunction in MDD along with a blood biomarker. Our work involves pericytes in the pathophysiology of mood disorders, highlights new therapeutic targets and provides tools to manipulate these cells applicable for vascular, neurodegenerative, or inflammatory diseases all characterized by high rates of depression.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-5060339/v1
- https://www.researchsquare.com/article/rs-5060339/latest.pdf
- OA Status
- gold
- Cited By
- 5
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4403237536
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4403237536Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-5060339/v1Digital Object Identifier
- Title
-
Pericytes modulate brain vascular integrity in social stress and depressionWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-10-08Full publication date if available
- Authors
-
Caroline Ménard, Laurence Dion‐Albert, Alice Cadoret, José L. Solano, Pavel Kotchetkov, Luca Pancotti, Sam E.J. Paton, Jared VanderZwaag, Adeline Collignon, Luisa Bandeira Binder, Raleigh M. Linville, Émanuelle Richer, Manon Lebel, Signature Consortium, Myriam Heiman, Marie‐Ève Tremblay, Christophe D. Proulx, Gustavo Turecki, Naguib Mechawar, Baptiste LacosteList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-5060339/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-5060339/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-5060339/latest.pdfDirect OA link when available
- Concepts
-
Depression (economics), Stress (linguistics), Neuroscience, Psychology, Business, Economics, Macroeconomics, Philosophy, LinguisticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
5Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 1Per-year citation counts (last 5 years)
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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