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Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility

ABSTRACT: Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility

PROVIDER: PRJNA836902 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19159301_1.fastq.gz	Fastqsanger.gz
	SRR19159301_2.fastq.gz	Fastqsanger.gz
	SRR19159302_1.fastq.gz	Fastqsanger.gz
	SRR19159302_2.fastq.gz	Fastqsanger.gz
	SRR19159303_1.fastq.gz	Fastqsanger.gz

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Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility

Project description:Psychosocial stress has profound effects on the body, including the peripheral immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3,4,5, the underlying mechanisms are not well understood. Here we show that a myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is elevated in serum from MDD subjects as well as in stress susceptible (SUS) mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), thereby altering social behavior. Using a combination of mass cytometry and single-cell RNA-sequencing, we performed high-dimensional phenotyping of immune cells in circulation and brain and demonstrate that peripheral monocytes are strongly affected by stress. Both peripheral and brain infiltrating monocytes of SUS mice show increased expression of Mmp8 following CSDS. We further show that peripheral MMP8 directly infiltrates the NAc parenchyma to control ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behavior and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a novel mechanism by which peripheral immune factors can affect central nervous system function and behavior in the context of stress. Targeting specific peripheral immune cell-derived proteins, such as matrix metalloproteinases, could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.

2023-02-24 | GSE202662 | GEO

Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility.

Project description:Psychosocial stress has profound effects on the body, including the peripheral immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3,4,5, the underlying mechanisms are not well understood. Here we show that a peripheral myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is elevated in serum of subjects with MDD as well as in stress-susceptible (SUS) mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), thereby altering social behaviour. Using a combination of mass cytometry and single-cell RNA-sequencing, we performed high-dimensional phenotyping of immune cells in circulation and brain and demonstrate that peripheral monocytes are strongly affected by stress. Both peripheral and brain-infiltrating monocytes of SUS mice showed increased Mmp8 expression following CSDS. We further demonstrate that peripheral MMP8 directly infiltrates the NAc parenchyma to control the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a novel mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.

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Matrix metalloproteinase-3 mediates cardiac differentiation of mouse embryonic stem cells

Project description:Recently, it was shown that the Bmp antagonist Noggin could strongly induce cardiomyocyte differentiation by transient treatment of undifferentiated ES cells. In order to determine how Noggin may induce cardiac differentiation, we compared differentially expressed genes during Noggin treatment of ES cells using microarray analysis and found that matrix metalloproteinase (Mmp)-3 is the only gene whose expression is increased by Noggin treatment. Keywords: embryonic stem cells, cardiac differentiation, matrix metalloproteinase-3, Noggin

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Increased plasma matrix metalloproteinase 1 is associated with the presence of esophageal squamous cell carcinoma

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Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote re-epithelialization of diabetic wounds

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A matrix metalloproteinase biosensor-functionalized metastasis-on-a-chip platform for evaluating adrenocortical carcinoma progression

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