16 research outputs found
Recommended from our members
Social stress alters splenocyte phenotype and function
Social stress of group-housed male mice induced a state of functional glucocorticoid (GC) resistance in splenocytes. The following studies examined the effects of paired-fighting (PF) stress on immune cell distribution and function in spleens of male mice. Following six daily PF stress sessions, splenic monocytes and neutrophils increased and lymphocytes decreased. PF also altered the distribution of CD62L and CD11b positive monocytes. Additionally, PF augmented proliferation and lowered the sensitivity of LPS-stimulated splenocytes to the antiproliferative effects of corticosterone, suggesting that PF induced a state of GC resistance in splenocytes. Together, these findings indicate that social stress altered phenotype and function of splenic immune cells. These findings may have implications for the healing of bite wounds that are often associated with social stress in rodents
Recommended from our members
Social experience alters the response to social stress in mice
Individual differences in the response to stressful stimuli have been documented in humans and in a variety of animal species. Recently, we demonstrated that social stress induced a state of glucocorticoid (GC) resistance in mouse splenocytes, however this response was highly variable among cage mates. Since these studies were conducted using inbred mice (C57BL/6), it was suggested that environmental factors were the source of this variability. The following study examined possible factors that may have contributed to the development of individual differences in the susceptibility of mice to social stress. First, the effect of rearing conditions was studied by comparing the development of GC resistance in mice reared in isolation or in groups. In addition, the effect of previous social experiences was studied in mice that were re-housed to facilitate the formation of new social hierarchies in the cages. The results indicated that isolation altered the behavior of the mice during the social stress, but did not affect the development of GC resistance in response to the stress. Re-housing and the resulting loss of social status increased the susceptibility of mice to the development of GC resistance following social stress. Together, these findings indicate that environmental factors, such as previous social experiences, may alter the susceptibility to the effects of future social stress in inbred mice
Recommended from our members
Social disruption-induced glucocorticoid resistance: kinetics and site specificity
Social disruption (SDR) of male mice has been shown to induce a state of functional glucocorticoid (GC) resistance in splenocytes. The present study demonstrated that GC resistance developed following repeated, but not acute exposure to SDR. GC resistance was long-lasting and persisted for at least 10 days after stress. In contrast, SDR did not alter cytokine secretion from peritoneal mononuclear cells treated with corticosterone. These findings suggest that SDR-induced GC resistance may be restricted to specific sites such as the spleen
Recommended from our members
Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice
Splenocytes from socially stressed male mice display functional glucocorticoid (GC) resistance, viz., the antiproliferative effects of GC on lipopolysaccharide (LPS)-stimulated splenocytes is absent. In this study, we investigated changes in the structure and function of the glucocorticoid receptor (GR) in socially stressed animals. Changes of GR at both DNA and RNA levels were excluded. Reduced GR function was restricted to macrophages (CD11b
+) in association with impaired nuclear translocation of GR after GC stimulation. Consequently, GC failed to block the activation of NF-κB in these cells. Thus, impaired nuclear translocation of GR and the lack of transcriptional suppression of NF-κB by GC were identified as the molecular mechanisms responsible for the observed GC resistance in spleens of socially stressed mice
Recommended from our members
Expression of glucocorticoid resistance following social stress requires a second signal
Stimulation of splenocytes from socially stressed mice [social disruption (SDR)] with Gram-negative bacterial lipopolysaccharide (LPS) revealed a state of functional glucocorticoid (GC) resistance. LPS-stimulated splenocytes were less sensitive to the inhibitory effects of corticosterone. This study demonstrated that activation signals were required for the expression of splenic GC resistance. The results demonstrated that six cycles of SDR induced splenomegaly and increased the number of CD11b-positive monocytes. SDR also increased the viability of cultured, nonstimulated splenocytes, and addition of corticosterone reduced the viability of these cells in a dose-dependent manner. However, following stimulation with LPS, the sensitivity of SDR splenocytes to GC was reduced. Similar results were obtained using lipid A, a fraction of the LPS molecule that binds to Toll-like receptor (TLR)4. Furthermore, C3H/HeJ mice that do not possess a functional TLR4 molecule responded to SDR with an increased number of CD11b-positive monocytes in the spleen and increased viability of nonstimulated splenocytes. However, neither LPS nor lipid A stimulation resulted in the expression of GC resistance. Together, these findings suggest that the expression of GC resistance in response to SDR requires a second signal that can be provided by ligation of TLR4