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Sex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. Using Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced > 5 % reduction in Body Mass Index (BMI) over four years. Using a previously validated deep-learning algorithm, we measured Magnetic Resonance Imaging (MRI)-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. A retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5 % of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: −9.72 ± 4.38, males: −8.83 ± 3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95 %CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95 %CI: −3.9 %/4-year, −6.5 to −1.4, P-value=0.019). In participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss. [ABSTRACT FROM AUTHOR]

Research has demonstrated that chronic stress experienced early in life can lead to impairments in memory and learning. These deficits are attributed to an imbalance in the interaction between glucocorticoids, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoid receptors in brain regions responsible for mediating memory, such as the hippocampus. This imbalance can result in detrimental conditions like neuroinflammation. The aim of this study was to assess the impact of sumatriptan, a selective agonist for 5-HT 1B/1D receptors, on fear learning capabilities in a chronic social isolation stress model in mice, with a particular focus on the role of the HPA axis. Mice were assigned to two opposing conditions, including social condition (SC) and isolated condition (IC) for a duration of five weeks. All mice underwent passive avoidance test, with their subsequent freezing behavior serving as an indicator of fear retrieval. Mice in the IC group were administered either a vehicle, sumatriptan, GR-127935 (a selective antagonist for 5-HT 1B/1D receptors), or a combination of sumatriptan and GR-127935 during the testing sessions. At the end, all mice were sacrificed and samples of their serum and hippocampus were collected for further analysis. Isolation was found to significantly reduce freezing behavior (p<0.001). An increase in the freezing response among IC mice was observed following the administration of varying doses of sumatriptan, as indicated by a one-way ANOVA analysis (p<0.001). However, the mitigating effects of sumatriptan were reversed upon the administration of GR-127935. An ELISA assay conducted before and after the passive avoidance test revealed no significant change in serum corticosterone levels among SC mice. In contrast, a significant increase was observed among IC mice, suggesting hyper-responsiveness of the HPA axis in isolated animals. This hyper-responsiveness was ameliorated following the administration of sumatriptan. Furthermore, both the sumatriptan and SC groups exhibited a similar trend, showing a significant increase in the expression of hippocampal glucocorticoid receptors following the stress of the passive avoidance test. Lastly, the elevated production of inflammatory cytokines (TNF-α, IL-1β) observed following social isolation was attenuated in the sumatriptan group. Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation. [Display omitted] • It has been shown that chronic stress in early life could cause memory and learning disabilities. • Imbalance in HPA axis and glucocorticoid interaction in memory-related brain regions leads to neuroinflammation. • This study aimed to evaluate the effect of 5-HT 1B/1D receptor selective agonist, sumatriptan, on fear learning ability in a chronic socially isolated mice, considering the HPA axis role. • Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation. [ABSTRACT FROM AUTHOR]