Abstract
Cytokines in the brain, induced by various inflammatory challenges have been linked to sickness behaviors, including fatigue. However, the brain cytokine response to exercise is not well understood. Preliminary data show that exaggerated fatigue following downhill vs uphill running is associated with increased brain IL-1b concentration. PURPOSE: This study was designed to determine the role of brain macrophages in the increased IL-1b response to downhill running using a macrophage depletion technique involving ICV injection of clodronate-nlled liposomes (CLOD) that selectively targets perivascular and meningeal macrophages. METHODS: Male C57BL/6 mice (n=110) were assigned to 1 of 6 groups (UP-SAL, UP-CLOD, DWN-SAL, DWN-CLOD, CON-SAL & CON-CLOD). Initially mice were given lOuL ICV injections of either clodronate or saline-filled liposomes. Four days later, mice were run at 22 m/min and −14% or +14% grade, for 150-min. Con mice remained in their cages in the treadmill room. Fatigue was assessed 12–24hr later via voluntary wheel running (Exp. 1) or treadmill running to fatigue (Exp. 2). Brain IL-1b concentration was determined at 24-hr (Exp. 3). RESULTS: CLOD administration had no effect on any component (time, distance & peak speed) of wheel running (Exp 1), but did delay fatigue during treadmill running in both uphill (158 + 8 vs. 124 + 10 min) and downhill runners (126 + 15 vs. 65 + 8 min) compared to SAL (Exp 2). CLOD administration reduced IL-1b in the cortex of downhill runners (0.86 + 0.06 vs 1.05 + 0.1 pg/100ug total protein) and cerebellum of both uphill (3.5 + 0.2 vs. 4.1 + 0.18 pg/100ug total protein) and downhill runners (3.7 + 0.4 vs. 4.5 + 0.38 pg/100ug total protein) compared to SAL, but this effect didn't reach statistical significance (p=0.2). CONCLUSIONS: These results support a role of brain macrophages in some forms of fatigue, but the precise relationship between brain macrophages, IL-1b and central fatigue remain to be determined. This research was funded by a student research grant from the American College of Sports Medicine
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