Acute stress induces the rapid and transient induction of caspase-1, gasdermin D and release of constitutive IL-1β protein in dorsal hippocampus

The proinflammatory cytokine interleukin (IL)-1β plays a pivotal role in the behavioral manifestations (i.e., sickness) of the stress response. Indeed, exposure to acute and chronic stressors induces the expression of IL-1β in stress-sensitive brain regions. Thus, it is typically presumed that exposure to stressors induces the extra-cellular release of IL-1β in the brain parenchyma. However, this stress-evoked neuroimmune phenomenon has not been directly demonstrated nor has the cellular process of IL-1β release into the extracellular milieu been characterized in brain. This cellular process involves a form of inflammatory cell death, termed pyroptosis, which involves: 1) activation of caspase-1, 2) caspase-1 maturation of IL-1β, 3) caspase-1 cleavage of gasdermin D (GSDMD), and 4) GSDMD-induced permeability of the cell membrane through which IL-1β is released into the extracellular space. Thus, the present study examined whether stress induces the extra-cellular release of IL-1β and engages the above cellular process in mediating IL-1β release in the brain. Male Sprague-Dawley rats were exposed to inescapable tailshock (IS). IL-1β extra-cellular release, caspase-1 activity and cleavage of GSDMD were measured in dorsal hippocampus. We found that exposure to IS induced a transient increase in the release of IL-1β into the extracellular space immediately after termination of the stressor. IS also induced a transient increase in caspase-1 activity prior to IL-1β release, while activation of GSDMD was observed immediately after termination of the stressor. IS also increased mRNA and protein expression of the ESCRTIII protein CHMP4B, which is involved in cellular repair. The present results suggest that exposure to an acute stressor induces the hallmarks of pyroptosis in brain, which might serve as a key cellular process involved in the release of IL-1β into the extracellular milieu of the brain parenchyma.Matthew G.Frank, Michael V.Baratta, Kaixin Zhang, Isabella P.Fallon, Mikayleigh A.Pearson, Guozhen Liu ... et al

A critical exploration of lesbian perspectives on eating disorders

There is now a considerable body of research exploring how culturally dominant gendered norms are implicated in mobilising girls' and women's 'anorexic' and 'bulimic' experiences and practices. However, much less is known about lesbian experiences of 'eating disorders'. This article explores some of those specificities. Drawing on interviews with self-identified lesbian women with a history of 'anorexia' and/or 'bulimia', our analysis suggests that while many of the ways in which participants discursively constituted their 'eating disorders' were similar to those identified in research with girls and women assumed to be heterosexual, there were also important differences where participants' actual or emerging lesbian subjectivities were integral to their accounts of developing, living with and recovering from 'anorexia' and/or 'bulimia'. Our analysis suggests that the processes of coming to recognise oneself as a lesbian and of 'coming out' to others in predominantly hetero-normative contexts may be profoundly implicated in the discursive production of lesbian women's 'eating disorders' and that further research is required to better understand lesbian perspectives on 'eating disorders'. © 2013 Copyright Taylor and Francis Group, LLC