Mesenchymal Stromal Cells Modulate Peripheral Stress-Induced Innate Immune Activation Indirectly Limiting the Emergence of Neuroinflammation-Driven Depressive and Anxiety-like Behaviors.

BACKGROUND: Hyperactivation of innate immunity has been implicated in the etiology of mood disorders, including major depressive disorder (MDD). Mesenchymal stromal cells (MSCs) have demonstrated potent immunomodulatory capabilities in the context of chronic inflammatory disease and injury but have yet to be evaluated in stress-based preclinical models of MDD. We sought to test the ability of intravenous MSCs to modulate innate immune activation and behavioral patterns associated with repeated social defeat (RSD). METHODS: Murine RSD-induced innate immune activation as well as depressive and anxiety-like behaviors were assessed in unstressed, RSD, and RSD + human MSC groups. Biodistribution and fate studies were performed to inform potential mechanisms of action. RESULTS: MSCs reduced stress-induced circulating proinflammatory cytokines, monocytes, neuroinflammation, and depressive and anxiety-like behaviors. Biodistribution analyses indicated that infused MSCs distributed within peripheral organs without homing to the brain. Murine neutrophils targeted MSCs in the lungs within hours of administration. MSCs and recipient neutrophils were cleared by recipient macrophages promoting a switch toward a regulatory phenotype and systemic resolution of inflammation. CONCLUSIONS: Peripheral delivery of MSCs modulates central nervous system inflammatory processes and aberrant behavioral patterns in a stress-based rodent model of MDD and anxiety. Recent studies suggest that host immune cell-mediated phagocytosis of MSCs in vivo can trigger an immunomodulatory cascade, resulting in resolution of inflammation. Our data suggest that similar mechanisms may protect distal organs, including the brain, from systemic, stress-induced proinflammatory spikes and may uncover unexpected targets in the periphery for novel or adjunct treatment for a subset of patients with MDD.

Objectively Measured School Day Physical Activity Among Elementary Students in the United States and Finland.

BACKGROUND: Schools are in a unique position to ensure that all students meet the current physical activity (PA) recommendations. This study aimed to examine 1st to 3rd grade elementary students' accelerometer measured school day PA in the United States (U.S.) and Finland. METHODS: The sample consisted of 200 students (107 girls, 93 boys; ages 6 to 8) and their school day PA was monitored with hip-worn ActiGraph GT3X+ accelerometers across a 5-day school week and the thresholds 100 and 2296 count per minute were used to separate sedentary time, light PA, and moderate-to-vigorous PA (MVPA). RESULTS: On an average school day, students were engaged in MVPA for 20.0 min in the U.S. and 24.1 min in Finland. Students' school-day MVPA was 9 to 16 minutes higher during physical education (PE) days compared with non-PE days (U.S: 25.8 vs. 16.6 min/day; Finland: 36.3 vs. 20.1 min/day). Girls had less MVPA and more sedentary time compared with boys in both samples. CONCLUSION: This study highlights both the role of PE and other school day physical activities in meeting PA guidelines. Policy measures are needed to change the structure of the school day and enhance PA to ensure that students meet the PA recommendations.