Antidepressive properties of macrophage-colony stimulating factor in a mouse model of depression induced by chronic unpredictable stress

Previous studies have reported that macrophage-colony stimulating factor (M-CSF), a drug that is used to treat hematological system disease, can ameliorate chronic stress-induced depressive-like behaviors in mice. This indicates that M-CSF could be developed into a novel antidepressant. Here, we investigated the antidepressive properties of M-CSF, aiming to explore its potential values in depression treatment. Our results showed that a single M-CSF injection at the dose of 75 and 100 μg/kg, but not at 25 or 50 μg/kg, ameliorated chronic unpredictable stress (CUS)-induced depressive-like behaviors in mice at 5 h after the drug treatment. In a time-dependent experiment, a single M-CSF injection (100 μg/kg) was found to ameliorate the CUS-induced depressive-like behaviors in mice at 5 and 8 h, but not at 3 h, after the drug treatment. The antidepressant effect of the single M-CSF injection (100 μg/kg) in chronically-stressed mice persisted at least 10 days and disappeared at 14 days after the drug treatment. Moreover, 14 days after the first injection, a second M-CSF injection (100 μg/kg) still produced antidepressant effects at 5 h after the drug treatment in chronically-stressed mice who re-displayed depressive-like phenotypes. The antidepressant effect of M-CSF appeared to be mediated by the activation of the hippocampal microglia, as pre-inhibition of microglia by minocycline (40 mg/kg) or PLX3397 (290 mg/kg) pretreatment prevented the antidepressant effect of M-CSF in CUS mice. These results demonstrate that M-CSF produces rapid and sustained antidepressant effects via the activation of the microglia in the hippocampus in a dose- and time-dependent manner.