Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle—a muscle with mixed fiber type—but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P<0.01), while the vastus lateralis muscle mass was increased by 35% (P<0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P<0.001), but vastus lateralis (22% smaller, P<0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.

It is a well-known fact that DHEA declines on ageing and that it is linked to ageing-related neurodegeneration, which is characterised by gradual cognitive decline. Although DHEA is also associated with inflammation in the periphery, the link between DHEA and neuroinflammation in this context is less clear. This review drew from different bodies of literature to provide a more comprehensive picture of peripheral vs central endocrine shifts with advanced age—specifically in terms of DHEA. From this, we have formulated the hypothesis that DHEA decline is also linked to neuroinflammation and that increased localised availability of DHEA may have both therapeutic and preventative benefit to limit neurodegeneration. We provide a comprehensive discussion of literature on the potential for extragonadal DHEA synthesis by neuroglial cells and reflect on the feasibility of therapeutic manipulation of localised, central DHEA synthesis.

Although modern fluorescence microscopy produces detailed three-dimensional (3D) datasets, colocalization analysis and region of interest (ROI) selection is most commonly performed two-dimensionally (2D) using maximum intensity projections (MIP). However, these 2D projections exclude much of the available data. Furthermore, 2D ROI selections cannot adequately select complex 3D structures which may inadvertently lead to either the exclusion of relevant or the inclusion of irrelevant data points, consequently affecting the accuracy of the colocalization analysis. Using a virtual reality (VR) enabled system, we demonstrate that 3D visualization, sample interrogation and analysis can be achieved in a highly controlled and precise manner. We calculate several key colocalization metrics using both 2D and 3D derived super-resolved structured illumination-based data sets. Using a neuronal injury model, we investigate the change in colocalization between Tau and acetylated α-tubulin at control conditions, after 6 hours and again after 24 hours. We demonstrate that performing colocalization analysis in 3D enhances its sensitivity, leading to a greater number of statistically significant differences than could be established when using 2D methods. Moreover, by carefully delimiting the 3D structures under analysis using the 3D VR system, we were able to reveal a time dependent loss in colocalization between the Tau and microtubule network as an early event in neuronal injury. This behavior could not be reliably detected using a 2D based projection. We conclude that, using 3D colocalization analysis, biologically relevant samples can be interrogated and assessed with greater precision, thereby better exploiting the potential of fluorescence-based image analysis in biomedical research.

South African rooibos (Aspalathus linearis) tea is globally consumed for its health benefits and caffeine free nature, but no information is available on the neuroprotective capacity of (unfermented) green rooibos....

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