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Stu Sjouwerman, Founder and CEO of KnowBe4, Presented with Holland on the Hill Freddy Heineken Award

Stu Sjouwerman, Founder and CEO of KnowBe4, Presented with Holland on the Hill Freddy Heineken Award
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Stu Sjouwerman, Founder and CEO of KnowBe4, Presented with

Circulating myeloid-derived MMP8 in stress susceptibility and depression

Psychosocial stress has profound effects on the body, including the 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, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible 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), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly af

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