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

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

  • Neuropharmacology. 2020 Aug 1;172:108132. doi: 10.1016/j.neuropharm.2020.108132.
Ting Ye 1 Dan Wang 1 Zixuan Cai 1 Lijuan Tong 1 Zhuo Chen 2 Jiashu Lu 3 Xu Lu 1 Chao Huang 4 Xiaomei Yuan 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Nantong University, 19# Qixiu Road, Nantong, 226001, Jiangsu, China.
  • 2 Invasive Technology Department, Nantong First People's Hospital, The Second Affiliated Hospital of Nantong University, #6 North Road Hai'er Xiang, Nantong, 226001, Jiangsu, China.
  • 3 Department of Pharmacy, The People's Hospital of Taizhou, The Fifth Affiliated Hospital of Nantong University, #210 Yingchun Road, Taizhou, 225300, Jiangsu, China.
  • 4 Department of Pharmacology, School of Pharmacy, Nantong University, 19# Qixiu Road, Nantong, 226001, Jiangsu, China. Electronic address: huachao@ntu.edu.cn.
  • 5 Heart Failure Center, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, 610072, China. Electronic address: yuanxiaomei0903@126.com.
Abstract

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.

Keywords

Depression; Hippocampus; M-CSF; Microglia; Minocycline; PLX3397.

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