Exploring brain glutathione and peripheral blood markers in posttraumatic stress disorder: a combined [1H]MRS and peripheral blood study

IntroductionOxidative stress has been implicated in psychiatric disorders, including posttraumatic stress disorder (PTSD). Currently, the status of glutathione (GSH), the brain's most abundant antioxidant, in PTSD remains uncertain. Therefore, the current study investigated brain concentrations of GSH and peripheral concentrations of blood markers in individuals with PTSD vs. Healthy Controls (HC).MethodsGSH spectra was acquired in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) using MEGA-PRESS, a J-difference-editing acquisition method. Peripheral blood samples were analyzed for concentrations of metalloproteinase (MMP)-9, tissue inhibitors of MMP (TIMP)-1,2, and myeloperoxidase (MPO).ResultsThere was no difference in GSH between PTSD and HC in the ACC (n = 30 PTSD, n = 20 HC) or DLPFC (n = 14 PTSD, n = 18 HC). There were no group differences between peripheral blood markers (P > 0.3) except for (non-significantly) lower TIMP-2 in PTSD. Additionally, TIMP-2 and GSH in the ACC were positively related in those with PTSD. Finally, MPO and MMP-9 were negatively associated with duration of PTSD.ConclusionsWe do not report altered GSH concentrations in the ACC or DLPFC in PTSD, however, systemic MMPs and MPO might be implicated in central processes and progression of PTSD. Future research should investigate these relationships in larger sample sizes

Symbiotic Futures: Health, Well-being and Care in the Post-Covid World

The "Symbiotic Futures: Health, Well-being and Care in the Post-Covid World" project was jointly conceived by the Innovation School at Glasgow School of Art and the Institute of Cancer Sciences at the University of Glasgow. The project partnership involved a community of experts working across both organisations including the University of Glasgow’s new Mazumdar-Shaw Advanced Research Centre (ARC). Future experiences is a collaborative, futures-focused design project where students benefit from the input of a community of experts to design speculative future worlds and experiences based on research within key societal contexts. This iteration of the project asked the students to consider what happens in the Post-Covid landscape ten years from now, where symbiotic experiences of health, well-being and care have evolved to the extent that new forms of medical practice, health communities and cultures of care transform how we interact with each other, with professionals and the world around us. The GSA Innovation School’s final year BDes Product Design students and faculty formed a dynamic community of practice with health, wellbeing and care practitioners and researchers from The University of Glasgow and beyond. This gave the students the opportunity to reflect on the underlying complexities of the future of health, well-being and care, technological acceleration, human agency and quality of life, to envision a 2031 blueprint as a series of six future world exhibits, and design the products, services and system experiences for the people and environments within it. In the first part of the project (Stage 1), Future worlds are groups of students working together on specific topics, to establish the context for their project and collaborate on research and development. In this iteration of Future Experiences, the "Health, Well-being and Care" worlds were clustered together around ‘People focused’ and ‘Environment focused’, but also joined up across these groups to create pairs of worlds, and in the process generate symbiosis between the groups. These worlds were then the starting points which the students explored in their individual projects. The second part of the project (Stage 2) saw individual students select an aspect of their Future World research to develop as a design direction, which they then prototyped and produced as products, services, and/or systems. These are designed for specific communities, contexts or scenarios of use defined by the students to communicate a future experience. These Future experiences reflect the societal contexts explored during the research phase, projected 10 years into the future, and communicated in a manner that makes the themes engaging and accessible. The deposited materials are arranged as follows: 1. Project Landscape Map - A report and blueprint for the project that gives a visual overview of the structure and timeline of the project. 2. Stage one data folders - the data folders for stage one of the project are named after the themes the groups explored to create their Future Worlds. 3. Stage two data folders - the data folders for stage two of the project are named after the individual students who created the project

Concentration, distribution, and influence of aging on the 18 kDa translocator protein in human brain: Implications for brain imaging studies

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Investigating TSPO levels in occupation-related posttraumatic stress disorder

Abstract Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5–30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic–pituitary–adrenal-axis dysregulation and central immune response to trauma which warrants further study

Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief

International audienceTypically considered to be cell surface sensors of extracellular signals, heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) control many pathophysiological processes and are the target of 30% of therapeutic drugs. Activated receptors redistribute to endosomes, but researchers have yet to explore whether endosomal receptors generate signals that control complex processes in vivo and are viable therapeutic targets. We report that the substance P (SP) neurokinin 1 receptor (NK1R) signals from endosomes to induce sustained excitation of spinal neurons and pain transmission and that specific antagonism of the NK1R in endosomes with membrane-anchored drug conjugates providesmore effective and sustained pain relief than conventional plasmamembrane-targeted antagonists. Pharmacological and genetic disruption of clathrin, dynamin, and b-arrestin blocked SP-induced NK1R endocytosis and prevented SP-stimulated activation of cytosolic protein kinase C and nuclear extracellular signal-regulated kinase, as well as transcription. Endocytosis inhibitors prevented sustained SP-induced excitation of neurons in spinal cord slices in vitro and attenuated nociception in vivo. When conjugated to cholestanol to promote endosomal targeting, NK1R antagonists selectively inhibited endosomal signaling and sustained neuronal excitation. Cholestanol conjugation amplified and prolonged the antinociceptive actions of NK1R antagonists. These results reveal a critical role for endosomal signaling of the NK1R in the complex pathophysiology of pain and demonstrate the use of endosomally targeted GPCR antagonists