biostudies-literatureCathomas FSwiss National Science FoundationNIDDK NIH HHSNIDA NIH HHSNHLBI NIH HHSNIMH NIH HHSNIH HHS1108-1115https://www.ebi.ac.uk/biostudies/studies/S-EPMC10901735biostudies-literatureUnknown626(8001)Psychosocial stress has profound effects on the body, including the immune system and the brain^1,2. 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 ofNatureCirculating myeloid-derived MMP8 in stress susceptibility and depression.PMC10901735K99 DA058213S10 OD030463R01 MH051399S10 OD026880P01 HL131478R01 MH133299R01 MH114882R01 MH127820R01 MH129306P01 HL142494K99 DK137037R01 MH104559186708Ferrer-Perez CShen LParise EMDesland FMerad MLin HYChan KLWang JMurrough JWSowa ARahman AFernandez NAlvarez JMuhareb SJanssen WGCathomas FParise LFRamakrishnan ACampbell MLi LNestler EJSwirski FKRusso SJShimo YWilk CMCosti SDurand-de Cuttoli REstill MAubry AVKaster MPfalseCirculating myeloid-derived MMP8 in stress susceptibility and depression.Psychosocial stress has profound effects on the body, including the immune system and the brain^1,2. 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 of2024-01-01T00:00:00Z2024 Feb2026-07-15T09:52:04.392Z2024-11-09T06:18:14.767ZS-EPMC109017353832662210.1038/s41586-023-07015-2