S100a9 Protects Against the Effects of Repeated Social Defeat Stress

Repeated social defeat stress leads to immunometabolic shifts in innate immune cells of the spleen

“…All experimental mice were bred in house to eliminate shipping stress and microbiome shifts and co-housed with their littermates (≤5 mice per cage) prior to the start of experimentation to eliminate social isolation stress. CD-1 male retired breeder mice were obtained from Charles River Laboratories ( Moshfegh et al, 2022 ). Experimental mice were sacrificed by pentobarbital overdose (150 mg/kg, Fatal Plus, Vortech Pharmaceuticals, Dearborn, MI, USA) administered intraperitoneally.…”

“…Mice studied for scRNA-sequencing were a subset of a large cohort of mice ( Moshfegh et al, 2022 ) exposed to no stress (NS; n = 3 out of 33) or repeated social defeat stress (RSDS; n = 3 out of 32) conducted as previously published ( Moshfegh et al, 2019 , 2022 ; Elkhatib et al, 2020 , 2022 ). Briefly, RSDS mice were subjected to physical interactions with an unfamiliar, resident CD-1 aggressor ( Golden et al, 2011 ) for 5 min per day over 10 days.…”

“…After each session, experimental mice were housed in the social defeat cage on the opposite side of a clear perforated divider, allowing sensory contact with the aggressor over the next 24 h. NS mice were housed on either side of a divider and rotated similarly without being exposed to CD-1 aggressors. On Day 11, behavioral assessments were conducted (results reported in Moshfegh et al, 2022 ). Of note, in the larger cohort of mice from which the current study sample were drawn, RSDS was shown to decrease social interaction and induce anxiety-like behavior in the elevated plus maze test ( Moshfegh et al, 2022 ).…”

“…Using single cell (sc)RNA-Seq and bioenergetic assays we have previously shown that RSDS leads to profound immunometabolic changes in T cells of the spleen that included enhanced OXPHOS ( Moshfegh et al, 2022 ). To examine the immunometabolic impact of RSDS on myeloid cells, herein we analyzed scRNA-Seq data from a subset of non-stressed (NS) or RSDS mice that were part of a larger cohort in which mice displayed both behavioral and systemic inflammatory dysregulation following RSDS ( Moshfegh et al, 2022 ).…”

Defining the nuanced nature of redox biology in post-traumatic stress disorder

“…Additionally, work from our lab using a preclinical mouse model of PTSD known as repeated social defeat stress (RSDS) demonstrated that mitochondrial O 2 •- specifically in circulating and splenic T-lymphocytes is elevated immediately after psychological trauma and correlated with PTSD-like behaviors ( Moshfegh et al, 2019 ). Subsequent single cell RNA sequencing data revealed that T-lymphocytes isolated from stressed animals had a significant upregulation in gene expression pathways involved in oxidative phosphorylation and mitochondrial dysfunction, further highlighting the possible redox connection in immune cells in PTSD animal models ( Moshfegh et al, 2022 ). One possible reason these animal studies show strong redox signatures with psychological trauma compared to the human studies is the control of time after the traumatic incident.…”