Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model.

Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood-brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/ß-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain-blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/ß-catenin pathway.

Lasting scars: The impact of depression in early adulthood on subsequent labor market outcomes.

A growing body of evidence indicates that poor health early in life can leave lasting scars on adult health and economic outcomes. While much of this literature focuses on childhood experiences, mechanisms generating these lasting effects-recurrence of illness and interruption of human capital accumulation-are not limited to childhood. In this study, we examine how an episode of depression experienced in early adulthood affects subsequent labor market outcomes. We find that, at age 50, people who had met diagnostic criteria for depression when surveyed at ages 27-35 earn 10% lower hourly wages (conditional on occupation), work 120-180 fewer hours annually, and earn 24% lower annual wage incomes. A portion of this income penalty (21%-39%) occurs because depression is often a chronic condition, recurring later in life. But a substantial share (25%-55%) occurs because depression in early adulthood disrupts human capital accumulation, by reducing work experience and by influencing selection into occupations with skill distributions that offer lower potential for wage growth. These lingering effects of early depression reinforce the importance of early and multifaceted intervention to address depression and its follow-on effects in the workplace.

Lessons From the COVID-19 Pandemic on the Nature of Work Among Those With Mental Illness.

Workers with mental illness may be uniquely affected by the labor market impacts of the pandemic. The authors used data from the National Health Interview Survey (2016-2018) to categorize workers by employment in essential or nonessential industries and by the feasibility of working remotely. Workers with psychological distress prepandemic were less likely than those without psychological distress to have occupations where remote work was feasible. These individuals may face higher risk of exposure to the virus and, if they are nonessential workers, higher risk of unemployment. Efforts that facilitate safe, continued connection to the workforce may be of value to workers with preexisting mental illnesses.

Kininogen-Nitric Oxide Signaling at Nearby Nonexcited Acupoints after Long-Term Stimulation.

Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. We found that kininogen expression was significantly upregulated in the stimulated and the nonstimulated adjacent acupoints along the same meridian. The enhanced kininogen expression was meridian dependent and was most apparent among small vessels in the subcutaneous layer. Enhanced signals of nitric oxide synthases, cGMP-dependent protein kinase, and myosin light chain were also observed at the nonstimulated adjacent acupoints along the same meridian. These findings uncover biological changes at acupoints and suggest the critical role of the kininogen-nitric oxide signaling pathway in acupoint activation.